Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells - PubMed (original) (raw)
. 2000 Oct 1;89(7):1440-7.
Affiliations
- PMID: 11013356
Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells
T Schnelldorfer et al. Cancer. 2000.
Abstract
Background: Recent studies have demonstrated that various tumors express enhanced levels of the radical scavenger glutathione (GSH). Moreover, there are grounds for claiming that GSH plays a crucial role in cell proliferation and tumor resistance. In the current study, we investigated the relation between cell growth and GSH levels in the pancreatic adenocarcinoma cell line, AsPC-1, and the significance of GSH in tumor resistance to chemotherapy.
Methods: Cell growth in AsPC-1 was initiated through transforming growth factor-alpha (TGF-alpha) or fetal calf serum (FCS). Then, cell cycle, cell proliferation, and cellular GSH content were analyzed at different times in the presence or absence of buthionine sulfoximine (BSO). The impact of GSH on chemotherapy-induced apoptosis was studied using 5-fluorouracil or melphalan in the presence or absence of BSO. Finally, we compared the GSH content of 15 pancreatic tumor specimens with 10 normal pancreatic tissue specimens.
Results: Analysis of GSH in pancreatic tissues demonstrated increased GSH levels in cancerous compared with normal tissue (17.5 +/- 2.3 vs. 8. 8 +/- 1.4 nmol/mg protein; P < 0.004). Incubation of AsPC-1 with TGF-alpha or FCS resulted in cell proliferation and cell cycle activity, whereas GSH content was not altered. Incubation of GSH-depleted cells with TGF-alpha did not stimulate cell growth. In addition, GSH-depletion resulted in an increased rate of apoptosis after melphalan (6.3 +/- 0.3 % vs. 11.2 +/- 0.3 %; P < 0.001), but not after 5-fluorouracil treatment.
Conclusions: Taken together, our results show enhanced GSH levels in pancreatic carcinoma and an essential role of GSH in cell proliferation and in resistance of AsPC-1 cells. Therefore, GSH-depletion may improve the efficacy of adjuvant therapy in pancreatic carcinoma.
Similar articles
- Role of intracellular glutathione in cell sensitivity to the apoptosis induced by tumor necrosis factor {alpha}-related apoptosis-inducing ligand/anticancer drug combinations.
Meurette O, Lefeuvre-Orfila L, Rebillard A, Lagadic-Gossmann D, Dimanche-Boitrel MT. Meurette O, et al. Clin Cancer Res. 2005 Apr 15;11(8):3075-83. doi: 10.1158/1078-0432.CCR-04-1764. Clin Cancer Res. 2005. PMID: 15837763 - Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line.
Armstrong JS, Steinauer KK, Hornung B, Irish JM, Lecane P, Birrell GW, Peehl DM, Knox SJ. Armstrong JS, et al. Cell Death Differ. 2002 Mar;9(3):252-63. doi: 10.1038/sj.cdd.4400959. Cell Death Differ. 2002. PMID: 11859408 - Role of glutathione in cancer pathophysiology and therapeutic interventions.
Singh S, Khan AR, Gupta AK. Singh S, et al. J Exp Ther Oncol. 2012;9(4):303-16. J Exp Ther Oncol. 2012. PMID: 22545423 Review. - Glutathione in cancer biology and therapy.
Estrela JM, Ortega A, Obrador E. Estrela JM, et al. Crit Rev Clin Lab Sci. 2006;43(2):143-81. doi: 10.1080/10408360500523878. Crit Rev Clin Lab Sci. 2006. PMID: 16517421 Review.
Cited by
- Building on Cram's legacy: stimulated gating in hemicarcerands.
Liu F, Helgeson RC, Houk KN. Liu F, et al. Acc Chem Res. 2014 Jul 15;47(7):2168-76. doi: 10.1021/ar5001296. Epub 2014 May 6. Acc Chem Res. 2014. PMID: 24802979 Free PMC article. - Relationship of Oxidative Stress with HIV Disease Progression in HIV/HCV Co-infected and HIV Mono-infected Adults in Miami.
Shin DH, Martinez SS, Parsons M, Jayaweera DT, Campa A, Baum MK. Shin DH, et al. Int J Biosci Biochem Bioinforma. 2012;2(3):217-223. doi: 10.7763/ijbbb.2012.v2.104. Int J Biosci Biochem Bioinforma. 2012. PMID: 23504530 Free PMC article. - Synergistic apoptosis of CML cells by buthionine sulfoximine and hydroxychavicol correlates with activation of AIF and GSH-ROS-JNK-ERK-iNOS pathway.
Chowdhury AA, Chaudhuri J, Biswas N, Manna A, Chatterjee S, Mahato SK, Chaudhuri U, Jaisankar P, Bandyopadhyay S. Chowdhury AA, et al. PLoS One. 2013 Sep 9;8(9):e73672. doi: 10.1371/journal.pone.0073672. eCollection 2013. PLoS One. 2013. PMID: 24040019 Free PMC article. - Interfering with ROS Metabolism in Cancer Cells: The Potential Role of Quercetin.
Gibellini L, Pinti M, Nasi M, De Biasi S, Roat E, Bertoncelli L, Cossarizza A. Gibellini L, et al. Cancers (Basel). 2010 Jun 14;2(2):1288-311. doi: 10.3390/cancers2021288. Cancers (Basel). 2010. PMID: 24281116 Free PMC article. - NBD-based synthetic probes for sensing small molecules and proteins: design, sensing mechanisms and biological applications.
Jiang C, Huang H, Kang X, Yang L, Xi Z, Sun H, Pluth MD, Yi L. Jiang C, et al. Chem Soc Rev. 2021 Jul 5;50(13):7436-7495. doi: 10.1039/d0cs01096k. Chem Soc Rev. 2021. PMID: 34075930 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Medical