Targeting mitochondria for cancer therapy (original) (raw)
Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell100, 57–70 (2000). CASPubMed Google Scholar
Fulda, S. Tumor resistance to apoptosis. Int. J. Cancer124, 511–515 (2009). CASPubMed Google Scholar
Fulda, S. & Debatin, K. M. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene25, 4798–4811 (2006). CASPubMed Google Scholar
Kroemer, G., Galluzzi, L. & Brenner, C. Mitochondrial membrane permeabilization in cell death. Physiol. Rev.87, 99–163 (2007). CASPubMed Google Scholar
Galluzzi, L. et al. No death without life: vital functions of apoptotic effectors. Cell Death Differ.15, 1113–1123 (2008). CASPubMed Google Scholar
Galluzzi, L. & Kroemer, G. Necroptosis: a specialized pathway of programmed necrosis. Cell135, 1161–1163 (2008). CASPubMed Google Scholar
Golstein, P. & Kroemer, G. Cell death by necrosis: towards a molecular definition. Trends Biochem. Sci.32, 37–43 (2007). CASPubMed Google Scholar
Gogvadze, V., Orrenius, S. & Zhivotovsky, B. Mitochondria in cancer cells: what is so special about them? Trends Cell Biol.18, 165–173 (2008). CASPubMed Google Scholar
Bellance, N., Lestienne, P. & Rossignol, R. Mitochondria: from bioenergetics to the metabolic regulation of carcinogenesis. Front. Biosci.14, 4015–4034 (2009). Google Scholar
Diehn, M. et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature458, 780–783 (2009). First demonstration that breast cancer stem cells maintain lower levels of ROS than their non-tumorigenic counterparts, providing a link between the management of ROS by cancer stem cells and tumour resistance to radiotherapy. CASPubMedPubMed Central Google Scholar
Kroemer, G. & Pouyssegur, J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell13, 472–482 (2008). ArticleCASPubMed Google Scholar
Modica-Napolitano, J. S. & Singh, K. K. Mitochondrial dysfunction in cancer. Mitochondrion4, 755–762 (2004). CASPubMed Google Scholar
Canter, J. A., Kallianpur, A. R., Parl, F. F. & Millikan, R. C. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res.65, 8028–8033 (2005). CASPubMed Google Scholar
Petros, J. A. et al. mtDNA mutations increase tumorigenicity in prostate cancer. Proc. Natl Acad. Sci. USA102, 719–724 (2005). CASPubMedPubMed Central Google Scholar
Galluzzi, L. et al. Mitochondrial gateways to cancer. Mol. Aspects Med.31, 1–20 (2010). CASPubMed Google Scholar
Armstrong, J. S. Mitochondrial medicine: pharmacological targeting of mitochondria in disease. Br. J. Pharmacol.151, 1154–1165 (2007). CASPubMedPubMed Central Google Scholar
Galluzzi, L., Larochette, N., Zamzami, N. & Kroemer, G. Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene25, 4812–4830 (2006). CASPubMed Google Scholar
Gogvadze, V., Orrenius, S. & Zhivotovsky, B. Mitochondria as targets for cancer chemotherapy. Semin. Cancer Biol.19, 57–66 (2009). CASPubMed Google Scholar
Bouchier-Hayes, L., Munoz-Pinedo, C., Connell, S. & Green, D. R. Measuring apoptosis at the single cell level. Methods44, 222–228 (2008). CASPubMedPubMed Central Google Scholar
Nakagawa, T. et al. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature434, 652–658 (2005). CASPubMed Google Scholar
Baines, C. P., Kaiser, R. A., Sheiko, T., Craigen, W. J. & Molkentin, J. D. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nature Cell Biol.9, 550–555 (2007). CASPubMed Google Scholar
Galluzzi, L. & Kroemer, G. Mitochondrial apoptosis without VDAC. Nature Cell Biol.9, 487–489 (2007). CASPubMed Google Scholar
Kokoszka, J. E. et al. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature427, 461–465 (2004). CASPubMedPubMed Central Google Scholar
Majewski, N. et al. Hexokinase–mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol. Cell16, 819–830 (2004). CASPubMed Google Scholar
Zamora, M., Granell, M., Mampel, T. & Vinas, O. Adenine nucleotide translocase 3 (ANT3) overexpression induces apoptosis in cultured cells. FEBS Lett.563, 155–160 (2004). CASPubMed Google Scholar
Bauer, M. K., Schubert, A., Rocks, O. & Grimm, S. Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis. J. Cell Biol.147, 1493–1502 (1999). CASPubMedPubMed Central Google Scholar
Le Bras., M. et al. Chemosensitization by knockdown of adenine nucleotide translocase-2. Cancer Res.66, 9143–9152 (2006). CASPubMed Google Scholar
Marzo, I. et al. Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science281, 2027–2031 (1998). CASPubMed Google Scholar
Belzacq, A. S. et al. Bcl-2 and Bax modulate adenine nucleotide translocase activity. Cancer Res.63, 541–546 (2003). CASPubMed Google Scholar
Shen, Q. et al. Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans. Mol. Cell Biol.29, 3881–3893 (2009). CASPubMedPubMed Central Google Scholar
Zhivotovsky, B., Galluzzi, L., Kepp, O. & Kroemer, G. Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery. Cell Death Differ.16, 1419–1425 (2009). CASPubMed Google Scholar
Don, A. S. et al. A peptide trivalent arsenical inhibits tumor angiogenesis by perturbing mitochondrial function in angiogenic endothelial cells. Cancer Cell3, 497–509 (2003). Demonstrates that GSAO, a peptide trivalent arsenical that acts as an ANT cross-linker, inhibits tumour angiogenesis by selectively targeting mitochondria in proliferating endothelial cells. CASPubMed Google Scholar
Belzacq, A. S. et al. Adenine nucleotide translocator mediates the mitochondrial membrane permeabilization induced by lonidamine, arsenite and CD437. Oncogene20, 7579–7587 (2001). CASPubMed Google Scholar
Oudard, S. et al. Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme. J. Neurooncol.63, 81–86 (2003). PubMed Google Scholar
Dogliotti, L. et al. Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial. J. Clin. Oncol.14, 1165–1172 (1996). CASPubMed Google Scholar
Papaldo, P. et al. Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide. J. Clin. Oncol.21, 3462–3468 (2003). CASPubMed Google Scholar
Lehenkari, P. P. et al. Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol. Pharmacol.61, 1255–1262 (2002). CASPubMed Google Scholar
Diel, I. J. et al. Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann. Oncol.19, 2007–2011 (2008). CASPubMedPubMed Central Google Scholar
Green, J. R. Antitumor effects of bisphosphonates. Cancer97, 840–847 (2003). PubMed Google Scholar
Tang, X. et al. Bisphosphonates suppress insulin-like growth factor 1-induced angiogenesis via the HIF-1α/VEGF signaling pathways in human breast cancer cells. Int. J. Cancer126, 90–103 (2010). CASPubMedPubMed Central Google Scholar
Slack, J. L. & Rusiniak, M. E. Current issues in the management of acute promyelocytic leukemia. Ann. Hematol.79, 227–238 (2000). CASPubMed Google Scholar
Marchetti, P. et al. The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene carboxylic acid can trigger apoptosis through a mitochondrial pathway independent of the nucleus. Cancer Res.59, 6257–6266 (1999). CASPubMed Google Scholar
Notario, B., Zamora, M., Vinas, O. & Mampel, T. All-_trans_-retinoic acid binds to and inhibits adenine nucleotide translocase and induces mitochondrial permeability transition. Mol. Pharmacol.63, 224–231 (2003). CASPubMed Google Scholar
Parrella, E. et al. Antitumor activity of the retinoid-related molecules (E)-3-(4′-hydroxy-3′-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: role of retinoic acid receptor γ and retinoid-independent pathways. Mol. Pharmacol.70, 909–924 (2006). CASPubMed Google Scholar
Sala, F. et al. Development and validation of a liquid chromatography–tandem mass spectrometry method for the determination of ST1926, a novel oral antitumor agent, adamantyl retinoid derivative, in plasma of patients in a Phase I study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.877, 3118–3126 (2009). CASPubMed Google Scholar
Maaser, K. et al. Up-regulation of the peripheral benzodiazepine receptor during human colorectal carcinogenesis and tumor spread. Clin. Cancer Res.11, 1751–1756 (2005). CASPubMed Google Scholar
Galiegue, S., Casellas, P., Kramar, A., Tinel, N. & Simony-Lafontaine, J. Immunohistochemical assessment of the peripheral benzodiazepine receptor in breast cancer and its relationship with survival. Clin. Cancer Res.10, 2058–2064 (2004). CASPubMed Google Scholar
Okaro, A. C., Fennell, D. A., Corbo, M., Davidson, B. R. & Cotter, F. E. Pk11195, a mitochondrial benzodiazepine receptor antagonist, reduces apoptosis threshold in Bcl-XL and Mcl-1 expressing human cholangiocarcinoma cells. Gut51, 556–561 (2002). CASPubMedPubMed Central Google Scholar
Decaudin, D. et al. Peripheral benzodiazepine receptor ligands reverse apoptosis resistance of cancer cells in vitro and in vivo. Cancer Res.62, 1388–1393 (2002). CASPubMed Google Scholar
Gonzalez-Polo, R. A. et al. PK11195 potently sensitizes to apoptosis induction independently from the peripheral benzodiazepin receptor. Oncogene24, 7503–7513 (2005). CASPubMed Google Scholar
Walter, R. B. et al. PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism. Blood106, 3584–3593 (2005). CASPubMedPubMed Central Google Scholar
Palmeira, C. M. & Wallace, K. B. Benzoquinone inhibits the voltage-dependent induction of the mitochondrial permeability transition caused by redox-cycling naphthoquinones. Toxicol. Appl. Pharmacol.143, 338–347 (1997). CASPubMed Google Scholar
Petronilli, V. et al. The voltage sensor of the mitochondrial permeability transition pore is tuned by the oxidation-reduction state of vicinal thiols. Increase of the gating potential by oxidants and its reversal by reducing agents. J. Biol. Chem.269, 16638–16642 (1994). CASPubMed Google Scholar
Costantini, P. et al. Oxidation of a critical thiol residue of the adenine nucleotide translocator enforces Bcl-2-independent permeability transition pore opening and apoptosis. Oncogene19, 307–314 (2000). CASPubMed Google Scholar
Lim, D. et al. Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy. Invest. New Drugs23, 235–239 (2005). PubMed Google Scholar
Sarin, S. K. et al. High dose vitamin K3 infusion in advanced hepatocellular carcinoma. J. Gastroenterol. Hepatol.21, 1478–1482 (2006). CASPubMed Google Scholar
Magda, D. & Miller, R. A. Motexafin gadolinium: a novel redox active drug for cancer therapy. Semin. Cancer Biol.16, 466–476 (2006). CASPubMed Google Scholar
Mehta, M. P. et al. Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial. Int. J. Radiat. Oncol. Biol. Phys.73, 1069–1076 (2009). CASPubMed Google Scholar
Bradley, K. A. et al. Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a Children's Oncology Group phase I study. Neuro Oncol.10, 752–758 (2008). CASPubMedPubMed Central Google Scholar
Bey, E. A. et al. An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by β-lapachone. Proc. Natl Acad. Sci. USA104, 11832–11837 (2007). CASPubMedPubMed Central Google Scholar
Maeda, H. et al. Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine. Cell Death Differ.11, 737–746 (2004). CASPubMed Google Scholar
Dragovich, T. et al. Phase I trial of imexon in patients with advanced malignancy. J. Clin. Oncol.25, 1779–1784 (2007). CASPubMed Google Scholar
Moulder, S. et al. A phase I trial of imexon, a pro-oxidant, in combination with docetaxel for the treatment of patients with advanced breast, non-small cell lung and prostate cancer. Invest. New Drugs 6 Jun 2009 (doi:10.1007/s10637-009-9273-1). PubMed Google Scholar
Trachootham, D. et al. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate. Cancer Cell10, 241–252 (2006). Demonstrates that abnormal ROS generation in tumour cells can be exploited for selectively killing cancer versus normal cells by means of the natural compound PEITC. CASPubMed Google Scholar
Xiao, D. et al. Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential. Carcinogenesis27, 2223–2234 (2006). CASPubMed Google Scholar
Alexandre, J. et al. Improvement of the therapeutic index of anticancer drugs by the superoxide dismutase mimic mangafodipir. J. Natl Cancer Inst.98, 236–244 (2006). CASPubMed Google Scholar
Huang, P., Feng, L., Oldham, E. A., Keating, M. J. & Plunkett, W. Superoxide dismutase as a target for the selective killing of cancer cells. Nature407, 390–395 (2000). CASPubMed Google Scholar
Wood, L. et al. Inhibition of superoxide dismutase by 2-methoxyoestradiol analogues and oestrogen derivatives: structure–activity relationships. Anticancer Drug Des.16, 209–215 (2001). CASPubMed Google Scholar
Juarez, J. C. et al. Superoxide dismutase 1 (SOD1) is essential for H2O2-mediated oxidation and inactivation of phosphatases in growth factor signaling. Proc. Natl Acad. Sci. USA105, 7147–7152 (2008). CASPubMedPubMed Central Google Scholar
Lu, J., Chew, E. H. & Holmgren, A. Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc. Natl Acad. Sci. USA104, 12288–12293 (2007). CASPubMedPubMed Central Google Scholar
Tuma, R. S. Reactive oxygen species may have antitumor activity in metastatic melanoma. J. Natl Cancer Inst.100, 11–12 (2008). PubMed Google Scholar
Matei, D. et al. Activity of 2 methoxyestradiol (Panzem NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: a Hoosier Oncology Group trial. Gynecol. Oncol.115, 90–96 (2009). CASPubMed Google Scholar
Tevaarwerk, A. J. et al. Phase I trial of 2-methoxyestradiol NanoCrystal dispersion in advanced solid malignancies. Clin. Cancer Res.15, 1460–1465 (2009). CASPubMedPubMed Central Google Scholar
Rajkumar, S. V. et al. Novel therapy with 2-methoxyestradiol for the treatment of relapsed and plateau phase multiple myeloma. Clin. Cancer Res.13, 6162–6167 (2007). CASPubMed Google Scholar
Sweeney, C. et al. A phase II multicenter, randomized, double-blind, safety trial assessing the pharmacokinetics, pharmacodynamics, and efficacy of oral 2-methoxyestradiol capsules in hormone-refractory prostate cancer. Clin. Cancer Res.11, 6625–6633 (2005). CASPubMed Google Scholar
O'Day, S. et al. Phase II, randomized, controlled, double-blinded trial of weekly elesclomol plus paclitaxel versus paclitaxel alone for stage IV metastatic melanoma. J. Clin. Oncol.27, 5452–5458 (2009). CASPubMed Google Scholar
Berkenblit, A. et al. Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors. Clin. Cancer Res.13, 584–590 (2007). CASPubMed Google Scholar
Chipuk, J. E., Bouchier-Hayes, L. & Green, D. R. Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ.13, 1396–1402 (2006). CASPubMed Google Scholar
Willis, S. N. & Adams, J. M. Life in the balance: how BH3-only proteins induce apoptosis. Curr. Opin. Cell Biol.17, 617–625 (2005). CASPubMedPubMed Central Google Scholar
Lovell, J. F. et al. Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax. Cell135, 1074–1084 (2008). CASPubMed Google Scholar
Leu, J. I., Dumont, P., Hafey, M., Murphy, M. E. & George, D. L. Mitochondrial p53 activates Bak and causes disruption of a Bak–Mcl1 complex. Nature Cell Biol.6, 443–450 (2004). CASPubMed Google Scholar
Chipuk, J. E. et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science303, 1010–1014 (2004). CASPubMed Google Scholar
Bellot, G. et al. TOM22, a core component of the mitochondria outer membrane protein translocation pore, is a mitochondrial receptor for the proapoptotic protein Bax. Cell Death Differ.14, 785–794 (2007). CASPubMed Google Scholar
Ross, K., Rudel, T. & Kozjak-Pavlovic, V. TOM-independent complex formation of Bax and Bak in mammalian mitochondria during TNFα-induced apoptosis. Cell Death Differ.16, 697–707 (2009). CASPubMed Google Scholar
Rostovtseva, T. K. et al. Bax activates endophilin B1 oligomerization and lipid membrane vesiculation. J. Biol. Chem.284, 34390–34399 (2009). CASPubMedPubMed Central Google Scholar
Kuwana, T. et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell111, 331–342 (2002). CASPubMed Google Scholar
Lucken-Ardjomande, S., Montessuit, S. & Martinou, J. C. Contributions to Bax insertion and oligomerization of lipids of the mitochondrial outer membrane. Cell Death Differ.15, 929–937 (2008). CASPubMed Google Scholar
Cipolat, S. et al. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell126, 163–175 (2006). CASPubMed Google Scholar
Frezza, C. et al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell126, 177–189 (2006). CASPubMed Google Scholar
Lessene, G., Czabotar, P. E. & Colman, P. M. BCL-2 family antagonists for cancer therapy. Nature Rev. Drug Discov.7, 989–1000 (2008). CAS Google Scholar
Vogler, M., Dinsdale, D., Dyer, M. J. & Cohen, G. M. Bcl-2 inhibitors: small molecules with a big impact on cancer therapy. Cell Death Differ.16, 360–367 (2009). CASPubMed Google Scholar
Vogler, M. et al. Different forms of cell death induced by putative BCL2 inhibitors. Cell Death Differ.16, 1030–1039 (2009). CASPubMed Google Scholar
Oltersdorf, T. et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature435, 677–681 (2005). Describes the discovery of ABT-737, an inhibitor of BCL-2, BCL-XLand BCL-W, by nuclear magnetic resonance-based screening, parallel synthesis and structure-based design. CASPubMed Google Scholar
Chen, S., Dai, Y., Harada, H., Dent, P. & Grant, S. Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation. Cancer Res.67, 782–791 (2007). CASPubMed Google Scholar
Konopleva, M. et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell10, 375–388 (2006). CASPubMed Google Scholar
Mason, K. D. et al. In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas. Proc. Natl Acad. Sci. USA105, 17961–17966 (2008). CASPubMedPubMed Central Google Scholar
van Delft, M. F. et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell10, 389–399 (2006). CASPubMedPubMed Central Google Scholar
Kang, M. H. et al. Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo. Blood110, 2057–2066 (2007). CASPubMed Google Scholar
Kutuk, O. & Letai, A. Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed by ABT-737. Cancer Res.68, 7985–7994 (2008). CASPubMedPubMed Central Google Scholar
Hann, C. L. et al. Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer. Cancer Res.68, 2321–2328 (2008). CASPubMedPubMed Central Google Scholar
Tagscherer, K. E. et al. Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene27, 6646–6656 (2008). CASPubMed Google Scholar
Kuroda, J. et al. Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc. Natl Acad. Sci. USA103, 14907–14912 (2006). CASPubMedPubMed Central Google Scholar
Kuroda, J. et al. Apoptosis-based dual molecular targeting by INNO-406, a second-generation Bcr–Abl inhibitor, and ABT-737, an inhibitor of antiapoptotic Bcl-2 proteins, against Bcr–Abl-positive leukemia. Cell Death Differ.14, 1667–1677 (2007). CASPubMed Google Scholar
Kohl, T. M. et al. BH3 mimetic ABT-737 neutralizes resistance to FLT3 inhibitor treatment mediated by FLT3-independent expression of BCL2 in primary AML blasts. Leukemia21, 1763–1772 (2007). CASPubMed Google Scholar
Cragg, M. S., Kuroda, J., Puthalakath, H., Huang, D. C. & Strasser, A. Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics. PLoS Med.4, e316 (2007). PubMed Central Google Scholar
Gong, Y. et al. Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas. PLoS Med.4, e294 (2007). PubMedPubMed Central Google Scholar
Cragg, M. S. et al. Treatment of B-RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic. J. Clin. Invest.118, 3651–3659 (2008). CASPubMedPubMed Central Google Scholar
Paoluzzi, L. et al. The BH3-only mimetic ABT-737 synergizes the antineoplastic activity of proteasome inhibitors in lymphoid malignancies. Blood112, 2906–2916 (2008). CASPubMed Google Scholar
Miller, L. A. et al. BH3 mimetic ABT-737 and a proteasome inhibitor synergistically kill melanomas through Noxa-dependent apoptosis. J. Invest. Dermatol.129, 964–971 (2009). CASPubMed Google Scholar
Whitecross, K. F. et al. Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors. Blood113, 1982–1991 (2009). CASPubMed Google Scholar
Huang, S. & Sinicrope, F. A. BH3 mimetic ABT-737 potentiates TRAIL-mediated apoptotic signaling by unsequestering Bim and Bak in human pancreatic cancer cells. Cancer Res.68, 2944–2951 (2008). CASPubMedPubMed Central Google Scholar
Song, J. H., Kandasamy, K. & Kraft, A. S. ABT-737 induces expression of the death receptor 5 and sensitizes human cancer cells to TRAIL-induced apoptosis. J. Biol. Chem.283, 25003–25013 (2008). CASPubMedPubMed Central Google Scholar
Mason, K. D. et al. The BH3 mimetic compound, ABT-737, synergizes with a range of cytotoxic chemotherapy agents in chronic lymphocytic leukemia. Leukemia23, 2034–2041 (2009). CASPubMed Google Scholar
Tse, C. et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res.68, 3421–3428 (2008). CASPubMed Google Scholar
Lock, R. et al. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr. Blood Cancer50, 1181–1189 (2008). PubMed Google Scholar
Shoemaker, A. R. et al. A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo. Cancer Res.66, 8731–8739 (2006). CASPubMed Google Scholar
Lynn, A. & Jones, L. Gossypol and some other terpenoids, flavonoids, and phenols that affect quality of cottonseed protein. Am. Oil Chemists Soc.56, 727–730 (1979). Google Scholar
Azmi, A. S. & Mohammad, R. M. Non-peptidic small molecule inhibitors against Bcl-2 for cancer therapy. J. Cell Physiol.218, 13–21 (2009). CASPubMedPubMed Central Google Scholar
Liu, G. et al. An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin. Cancer Res.15, 3172–3176 (2009). CASPubMedPubMed Central Google Scholar
Kitada, S. et al. Bcl-2 antagonist apogossypol (NSC736630) displays single-agent activity in Bcl-2-transgenic mice and has superior efficacy with less toxicity compared with gossypol (NSC19048). Blood111, 3211–3219 (2008). CASPubMedPubMed Central Google Scholar
Nguyen, M. et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc. Natl Acad. Sci. USA104, 19512–19517 (2007). First demonstration that obatoclax triggers apoptosis by neutralizing MCL1. CASPubMedPubMed Central Google Scholar
Trudel, S. et al. Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myeloma. Blood109, 5430–5438 (2007). CASPubMed Google Scholar
Perez-Galan, P., Roue, G., Villamor, N., Campo, E. & Colomer, D. The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak. Blood109, 4441–4449 (2007). CASPubMed Google Scholar
Konopleva, M. et al. Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax). Cancer Res.68, 3413–3420 (2008). CASPubMedPubMed Central Google Scholar
O'Brien, S. M. et al. Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia. Blood113, 299–305 (2009). CASPubMedPubMed Central Google Scholar
Schimmer, A. D. et al. A phase I study of the pan bcl-2 family inhibitor obatoclax mesylate in patients with advanced hematologic malignancies. Clin. Cancer Res.14, 8295–8301 (2008). CASPubMed Google Scholar
Wang, J. L. et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc. Natl Acad. Sci. USA97, 7124–7129 (2000). CASPubMedPubMed Central Google Scholar
Manero, F. et al. The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death. Cancer Res.66, 2757–2764 (2006). CASPubMed Google Scholar
Moulder, S. L. et al. Phase I/II study of G3139 (Bcl-2 antisense oligonucleotide) in combination with doxorubicin and docetaxel in breast cancer. Clin. Cancer Res.14, 7909–7916 (2008). CASPubMedPubMed Central Google Scholar
O'Brien, S. et al. Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (Bcl-2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia. J. Clin. Oncol.25, 1114–1120 (2007). CASPubMed Google Scholar
Rheingold, S. R. et al. Phase I Trial of G3139, a bcl-2 antisense oligonucleotide, combined with doxorubicin and cyclophosphamide in children with relapsed solid tumors: a Children's Oncology Group Study. J. Clin. Oncol.25, 1512–1518 (2007). CASPubMed Google Scholar
Rudin, C. M. et al. Randomized phase II Study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103. J. Clin. Oncol.26, 870–876 (2008). CASPubMed Google Scholar
Chanan-Khan, A. A. et al. Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma. Leuk. Lymphoma50, 559–565 (2009). CASPubMed Google Scholar
Simons, A. L., Ahmad, I. M., Mattson, D. M., Dornfeld, K. J. & Spitz, D. R. 2-Deoxy-D-glucose combined with cisplatin enhances cytotoxicity via metabolic oxidative stress in human head and neck cancer cells. Cancer Res.67, 3364–3370 (2007). CASPubMed Google Scholar
Pastorino, J. G., Hoek, J. B. & Shulga, N. Activation of glycogen synthase kinase 3β disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res.65, 10545–10554 (2005). CASPubMed Google Scholar
Chiara, F. et al. Hexokinase II detachment from mitochondria triggers apoptosis through the permeability transition pore independent of voltage-dependent anion channels. PLoS One3, e1852 (2008). PubMedPubMed Central Google Scholar
Galluzzi, L., Kepp, O., Tajeddine, N. & Kroemer, G. Disruption of the hexokinase-VDAC complex for tumor therapy. Oncogene27, 4633–4635 (2008). CASPubMed Google Scholar
Goldin, N. et al. Methyl jasmonate binds to and detaches mitochondria-bound hexokinase. Oncogene27, 4636–4643 (2008). CASPubMed Google Scholar
Kim, W. et al. Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma. Mol. Cancer Ther.6, 2554–2562 (2007). CASPubMed Google Scholar
Cao, X. et al. Synergistic antipancreatic tumor effect by simultaneously targeting hypoxic cancer cells with HSP90 inhibitor and glycolysis inhibitor. Clin. Cancer Res.14, 1831–1839 (2008). CASPubMed Google Scholar
Chen, Z., Zhang, H., Lu, W. & Huang, P. Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate. Biochim. Biophys. Acta1787, 553–560 (2009). CASPubMedPubMed Central Google Scholar
Bonnet, S. et al. A mitochondria–K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell11, 37–51 (2007). Proof-of-concept study that the PDK inhibitor dichloroacetate induces apoptosis by shifting metabolism from glycolysis to glucose oxidation (resulting in mitochondrial depolarization), and by upregulating the K+ channel Kv1.5. CASPubMed Google Scholar
Fantin, V. R., St-Pierre, J. & Leder, P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell9, 425–434 (2006). CASPubMed Google Scholar
Hatzivassiliou, G. et al. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell8, 311–321 (2005). CASPubMed Google Scholar
Wellen, K. E. et al. ATP-citrate lyase links cellular metabolism to histone acetylation. Science324, 1076–1080 (2009). Identification of a novel molecular link between cellular metabolism and gene regulation through histone acetylation. CASPubMedPubMed Central Google Scholar
Beckers, A. et al. Chemical inhibition of acetyl-CoA carboxylase induces growth arrest and cytotoxicity selectively in cancer cells. Cancer Res.67, 8180–8187 (2007). CASPubMed Google Scholar
Carvalho, M. A. et al. Fatty acid synthase inhibition with Orlistat promotes apoptosis and reduces cell growth and lymph node metastasis in a mouse melanoma model. Int. J. Cancer123, 2557–2565 (2008). CASPubMed Google Scholar
Mootha, V. K. et al. Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell115, 629–640 (2003). CASPubMed Google Scholar
Kang, B. H. et al. Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network. Cell131, 257–270 (2007). CASPubMed Google Scholar
Wright, G. L. et al. VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase. FASEB J.22, 3264–3275 (2008). CASPubMedPubMed Central Google Scholar
Plescia, J. et al. Rational design of shepherdin, a novel anticancer agent. Cancer Cell7, 457–468 (2005). Development of the first cell-permeable peptidomimetic that disrupts the interaction between the chaperone HSP90 and the anti-apoptotic and mitotic regulator survivin. CASPubMed Google Scholar
Gyurkocza, B. et al. Antileukemic activity of shepherdin and molecular diversity of hsp90 inhibitors. J. Natl Cancer Inst.98, 1068–1077 (2006). CASPubMed Google Scholar
Kang, B. H. et al. Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90. J. Clin. Invest.119, 454–464 (2009). CASPubMedPubMed Central Google Scholar
Rodina, A. et al. Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Nature Chem. Biol.3, 498–507 (2007). CAS Google Scholar
Caldas-Lopes, E. et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc. Natl Acad. Sci. USA106, 8368–8373 (2009). CASPubMedPubMed Central Google Scholar
Paduch, R., Kandefer-Szerszen, M., Trytek, M. & Fiedurek, J. Terpenes: substances useful in human healthcare. Arch. Immunol. Ther. Exp. (Warsz)55, 315–327 (2007). CAS Google Scholar
Liby, K. T., Yore, M. M. & Sporn, M. B. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nature Rev. Cancer7, 357–369 (2007). CAS Google Scholar
Cichewicz, R. H. & Kouzi, S. A. Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med. Res. Rev.24, 90–114 (2004). CASPubMed Google Scholar
Fulda, S. et al. Betulinic acid triggers CD95 (APO-1/Fas)- and p53-independent apoptosis via activation of caspases in neuroectodermal tumors. Cancer Res.57, 4956–4964 (1997). CASPubMed Google Scholar
Fulda, S. et al. Activation of mitochondria and release of mitochondrial apoptogenic factors by betulinic acid. J. Biol. Chem.273, 33942–33948 (1998). CASPubMed Google Scholar
Fulda, S., Susin, S. A., Kroemer, G. & Debatin, K. M. Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells. Cancer Res.58, 4453–4460 (1998). CASPubMed Google Scholar
Andre, N. et al. Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells. FEBS Lett.532, 256–260 (2002). CASPubMed Google Scholar
Wick, W., Grimmel, C., Wagenknecht, B., Dichgans, J. & Weller, M. Betulinic acid-induced apoptosis in glioma cells: A sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing. J. Pharmacol. Exp. Ther.289, 1306–1312 (1999). CAS Google Scholar
Tan, Y., Yu, R. & Pezzuto, J. M. Betulinic acid-induced programmed cell death in human melanoma cells involves mitogen-activated protein kinase activation. Clin. Cancer Res.9, 2866–2875 (2003). CASPubMed Google Scholar
Selzer, E. et al. Effects of betulinic acid alone and in combination with irradiation in human melanoma cells. J. Invest. Dermatol.114, 935–940 (2000). CASPubMed Google Scholar
Selzer, E. et al. Betulinic acid-induced Mcl-1 expression in human melanoma — mode of action and functional significance. Mol. Med.8, 877–884 (2002). CASPubMedPubMed Central Google Scholar
Thurnher, D. et al. Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells. Head Neck25, 732–740 (2003). PubMed Google Scholar
Fulda, S. & Debatin, K. M. Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors. Med. Pediatr. Oncol.35, 616–618 (2000). CASPubMed Google Scholar
Meng, R. D. & El-Deiry, W. S. p53-independent upregulation of KILLER/DR5 TRAIL receptor expression by glucocorticoids and interferon-gamma. Exp. Cell Res.262, 154–169 (2001). CASPubMed Google Scholar
Salti, G. I. et al. Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital melanocytic naeval cells: evidence for a potential role as a chemopreventive agent. Melanoma Res.11, 99–104 (2001). CASPubMed Google Scholar
Zuco, V. et al. Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells. Cancer Lett.175, 17–25 (2002). CASPubMed Google Scholar
Lagouge, M. et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell127, 1109–1122 (2006). CASPubMed Google Scholar
Gledhill, J. R., Montgomery, M. G., Leslie, A. G. & Walker, J. E. Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proc. Natl Acad. Sci. USA104, 13632–13637 (2007). CASPubMedPubMed Central Google Scholar
Tinhofer, I. et al. Resveratrol, a tumor-suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl-2. FASEB J.15, 1613–1615 (2001). CASPubMed Google Scholar
Chen, C. et al. Mitochondrial ATP synthasome: three-dimensional structure by electron microscopy of the ATP synthase in complex formation with carriers for Pi and ADP/ATP. J. Biol. Chem.279, 31761–31768 (2004). CASPubMed Google Scholar
Biasutto, L. et al. Development of mitochondria-targeted derivatives of resveratrol. Bioorg Med. Chem. Lett.18, 5594–5597 (2008). CASPubMed Google Scholar
Jeong, S. H. et al. A novel resveratrol derivative, HS1793, overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells. Biochem. Pharmacol.77, 1337–1347 (2009). CASPubMed Google Scholar
Morrison, D. K. The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol.19, 16–23 (2009). CASPubMed Google Scholar
Korsmeyer, S. J. BCL-2 gene family and the regulation of programmed cell death. Cancer Res.59, 1693s–1700s (1999). CASPubMed Google Scholar
Boocock, D. J. et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol. Biomarkers Prev.16, 1246–1252 (2007). CASPubMed Google Scholar
Constantinou, C., Papas, A. & Constantinou, A. I. Vitamin E and cancer: an insight into the anticancer activities of vitamin E isomers and analogs. Int. J. Cancer123, 739–752 (2008). CASPubMed Google Scholar
Zhao, Y., Neuzil, J. & Wu, K. Vitamin E analogues as mitochondria-targeting compounds: from the bench to the bedside? Mol. Nutr. Food Res.53, 129–139 (2009). CASPubMed Google Scholar
Jia, L., Yu, W., Wang, P., Sanders, B. G. & Kline, K. In vivo and in vitro studies of anticancer actions of α-TEA for human prostate cancer cells. Prostate68, 849–860 (2008). CASPubMed Google Scholar
Hahn, T. et al. Dietary administration of the proapoptotic vitamin E analogue α-tocopheryloxyacetic acid inhibits metastatic murine breast cancer. Cancer Res.66, 9374–9378 (2006). CASPubMed Google Scholar
Lawson, K. A. et al. Comparison of vitamin E derivatives α-TEA and VES in reduction of mouse mammary tumor burden and metastasis. Exp. Biol. Med. (Maywood)229, 954–963 (2004). CAS Google Scholar
Dong, L. F. et al. Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II. Oncogene27, 4324–4335 (2008). Identification of the interaction with the proximal and distal ubiquinone-binding sites of the respiratory complex II as the molecular basis for the mitochondrial targeting of α-TOS. CASPubMedPubMed Central Google Scholar
Dong, L. F. et al. Suppression of tumor growth in vivo by the mitocan α-tocopheryl succinate requires respiratory complex II. Clin. Cancer Res.15, 1593–1600 (2009). CASPubMed Google Scholar
Dong, L. F. et al. Vitamin E analogues inhibit angiogenesis by selective induction of apoptosis in proliferating endothelial cells: the role of oxidative stress. Cancer Res.67, 11906–11913 (2007). CASPubMed Google Scholar
Neuzil, J. et al. Induction of cancer cell apoptosis by α-tocopheryl succinate: molecular pathways and structural requirements. FASEB J.15, 403–415 (2001). CASPubMed Google Scholar
Fariss, M. W., Nicholls-Grzemski, F. A., Tirmenstein, M. A. & Zhang, J. G. Enhanced antioxidant and cytoprotective abilities of vitamin E succinate is associated with a rapid uptake advantage in rat hepatocytes and mitochondria. Free Radic. Biol. Med.31, 530–541 (2001). CASPubMed Google Scholar
Wright, M. E. et al. Effects of α-tocopherol and β-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial. Cancer109, 891–898 (2007). CASPubMed Google Scholar
Kim, J. H. et al. Susceptibility of cholangiocarcinoma cells to parthenolide-induced apoptosis. Cancer Res.65, 6312–6320 (2005). CASPubMed Google Scholar
Steele, A. J. et al. The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro. Leukemia20, 1073–1079 (2006). CASPubMed Google Scholar
Zhang, S., Ong, C. N. & Shen, H. M. Involvement of proapoptotic Bcl-2 family members in parthenolide-induced mitochondrial dysfunction and apoptosis. Cancer Lett.211, 175–188 (2004). CASPubMed Google Scholar
Guzman, M. L. et al. An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells. Blood110, 4427–4435 (2007). CASPubMedPubMed Central Google Scholar
Guzman, M. L. et al. The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood105, 4163–4169 (2005). CASPubMedPubMed Central Google Scholar
Pajak, B., Gajkowska, B. & Orzechowski, A. Molecular basis of parthenolide-dependent proapoptotic activity in cancer cells. Folia Histochem. Cytobiol.46, 129–135 (2008). CASPubMed Google Scholar
Rosen, J. M. & Jordan, C. T. The increasing complexity of the cancer stem cell paradigm. Science324, 1670–1673 (2009). CASPubMedPubMed Central Google Scholar
Smith, J., Ladi, E., Mayer-Proschel, M. & Noble, M. Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell. Proc. Natl Acad. Sci. USA97, 10032–10037 (2000). CASPubMedPubMed Central Google Scholar
Tsatmali, M., Walcott, E. C. & Crossin, K. L. Newborn neurons acquire high levels of reactive oxygen species and increased mitochondrial proteins upon differentiation from progenitors. Brain Res.1040, 137–150 (2005). CASPubMed Google Scholar
Ito, K. et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature431, 997–1002 (2004). CASPubMed Google Scholar
Ito, K. et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nature Med.12, 446–451 (2006). CASPubMed Google Scholar
Tothova, Z. et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell128, 325–339 (2007). CASPubMed Google Scholar
Miyamoto, K. et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell1, 101–112 (2007). CASPubMed Google Scholar
Simon, M. C. & Keith, B. The role of oxygen availability in embryonic development and stem cell function. Nature Rev. Mol. Cell Biol.9, 285–296 (2008). CAS Google Scholar
Brahimi-Horn, M. C., Chiche, J. & Pouyssegur, J. Hypoxia signalling controls metabolic demand. Curr. Opin. Cell Biol.19, 223–229 (2007). CASPubMed Google Scholar
Warburg, O., Posener, K. & Negelein, E. Über den Stoffwechsel der Tumoren. Biochemische Zeitschrift152, 319–344 (1924) (in German). Google Scholar
Miyamoto, S., Murphy, A. N. & Brown, J. H. Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ.15, 521–529 (2008). CASPubMed Google Scholar
Wang, H. Q. et al. Positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells. Oncogene24, 3574–3582 (2005). CASPubMed Google Scholar
Christofk, H. R., Vander Heiden, M. G., Wu, N., Asara, J. M. & Cantley, L. C. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature452, 181–186 (2008). CASPubMed Google Scholar
Bensaad, K. et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell126, 107–120 (2006). CASPubMed Google Scholar
Matoba, S. et al. p53 regulates mitochondrial respiration. Science312, 1650–1653 (2006). This is the first demonstration that the absence of a single p53 target gene, synthesis of SCO2, recapitulates the metabolic switch towards glycolysis that is exhibited by p53-deficient cells, thereby providing a possible explanation for the Warburg effect. CASPubMed Google Scholar
Kim, J. W., Tchernyshyov, I., Semenza, G. L. & Dang, C. V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell. Metab.3, 177–185 (2006). PubMed Google Scholar
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L. & Denko, N. C. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell. Metab.3, 187–197 (2006). CASPubMed Google Scholar
Gottlieb, E. & Tomlinson, I. P. Mitochondrial tumour suppressors: a genetic and biochemical update. Nature Rev. Cancer5, 857–866 (2005). CAS Google Scholar
Murphy, M. P. Selective targeting of bioactive compounds to mitochondria. Trends Biotechnol.15, 326–330 (1997). CASPubMed Google Scholar
Galluzzi, L. et al. Methods for the assessment of mitochondrial membrane permeabilization in apoptosis. Apoptosis12, 803–813 (2007). CASPubMed Google Scholar
Yousif, L. F., Stewart, K. M. & Kelley, S. O. Targeting mitochondria with organelle-specific compounds: strategies and applications. Chembiochem10, 1939–1950 (2009). CASPubMed Google Scholar
Ross, M. F., Filipovska, A., Smith, R. A., Gait, M. J. & Murphy, M. P. Cell-penetrating peptides do not cross mitochondrial membranes even when conjugated to a lipophilic cation: evidence against direct passage through phospholipid bilayers. Biochem. J.383, 457–468 (2004). CASPubMedPubMed Central Google Scholar
Kelso, G. F. et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J. Biol. Chem.276, 4588–4596 (2001). CASPubMed Google Scholar
Yousif, L. F., Stewart, K. M., Horton, K. L. & Kelley, S. O. Mitochondria-penetrating peptides: sequence effects and model cargo transport. Chembiochem10, 2081–2088 (2009). CASPubMed Google Scholar
Neupert, W. & Herrmann, J. M. Translocation of proteins into mitochondria. Annu. Rev. Biochem.76, 723–749 (2007). CASPubMed Google Scholar
Mukhopadhyay, A., Ni, L., Yang, C. S. & Weiner, H. Bacterial signal peptide recognizes HeLa cell mitochondrial import receptors and functions as a mitochondrial leader sequence. Cell. Mol. Life Sci.62, 1890–1899 (2005). CASPubMed Google Scholar
Vestweber, D. & Schatz, G. DNA–protein conjugates can enter mitochondria via the protein import pathway. Nature338, 170–172 (1989). CASPubMed Google Scholar
Srivastava, S. & Moraes, C. T. Manipulating mitochondrial DNA heteroplasmy by a mitochondrially targeted restriction endonuclease. Hum. Mol. Genet.10, 3093–3099 (2001). CASPubMed Google Scholar
Horton, K. L., Stewart, K. M., Fonseca, S. B., Guo, Q. & Kelley, S. O. Mitochondria-penetrating peptides. Chem. Biol.15, 375–382 (2008). CASPubMed Google Scholar
Maiti, K. K. et al. Guanidine-containing molecular transporters: sorbitol-based transporters show high intracellular selectivity toward mitochondria. Angew. Chem. Int. Ed. Engl.46, 5880–5884 (2007). CASPubMed Google Scholar
Yamada, Y. et al. MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion. Biochim. Biophys. Acta1778, 423–432 (2008). CASPubMed Google Scholar
Weissig, V. et al. DQAsomes: a novel potential drug and gene delivery system made from dequalinium. Pharm. Res.15, 334–337 (1998). CASPubMed Google Scholar
Galluzzi, L. et al. Methods to dissect mitochondrial membrane permeabilization in the course of apoptosis. Methods Enzymol.442, 355–374 (2008). PubMed Google Scholar
Deniaud, A. et al. Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis. Oncogene27, 285–299 (2008). CASPubMed Google Scholar
Yamada, Y., Akita, H., Kogure, K., Kamiya, H. & Harashima, H. Mitochondrial drug delivery and mitochondrial disease therapy — an approach to liposome-based delivery targeted to mitochondria. Mitochondrion7, 63–71 (2007). CASPubMed Google Scholar
Sergeeva, A., Kolonin, M. G., Molldrem, J. J., Pasqualini, R. & Arap, W. Display technologies: application for the discovery of drug and gene delivery agents. Adv. Drug Deliv. Rev.58, 1622–1654 (2006). CASPubMedPubMed Central Google Scholar
Pathania, D., Millard, M. & Neamati, N. Opportunities in discovery and delivery of anticancer drugs targeting mitochondria and cancer cell metabolism. Adv. Drug Deliv. Rev.61, 1250–1275 (2009). CASPubMed Google Scholar
Kitada, S. et al. Discovery, characterization, and structure–activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins. J. Med. Chem.46, 4259–4264 (2003). CASPubMed Google Scholar
Kirshner, J. R. et al. Elesclomol induces cancer cell apoptosis through oxidative stress. Mol. Cancer Ther.7, 2319–2327 (2008). CASPubMed Google Scholar