Thalidomide protects endothelial cells from doxorubicin-induced apoptosis but alters cell morphology-reply to a rebuttal (original) (raw)
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Experimental and Clinical sciences
Phycobilisomes present in cyanobacteria are photosynthetic macromolecular protein complexes that are categorized into three types -phycoerythrins (high energy), phycocyanin (intermediate energy) and allophycocyanin (low energy). Structurally, they consist of α and β protein subunits and open chain tetrapyrrole prosthetic group (bilin chromophore), known for its antioxidant properties and therapeutic potential against a variety of physiological ailments. Phycoerythrins (C-PE) were purified from cyanobacterial strains Phormidium sp. A27DM and Halomicronema sp. A32DM and their respective apoptotic potentials were assessed on A549 human lung carcinoma cells. Both strains of cyanobacteria were cultured and the C-PE from each strain was extracted, quantified and characterized. C-PE accounted for a dose dependent decrement in cell viability, mitochondrial membrane potential and an increment in lactate dehydrogenase release. Higher doses of C-PE (of both strains) accounted for loss of cell viability and nuclear pycnosis. These findings were further substantiated with flow cytometry that revealed a cell arrest at G 0 /G 1 phase and a high percentage of cells undergoing apoptosis following C-PE treatment. These results confirm the efficacy of C-PE from Phormidium sp. or Halomicronema sp. in triggering apoptotic cell death. This study is the first to report on apoptotic property of C-PE against A549 human lung carcinoma cells and warrants further studies to establish its anti-cancer potential.
Possible Anticancer Activity of Rosuvastatine, Doxazosin, Repaglinide and Oxcarbazepin
Asian Pacific Journal of Cancer Prevention, 2014
Background: Rosuvastatine, doxazosin, repaglinide and oxcarbazepin are therapeutic drugs available in the market for the treatment of different diseases. Potential to display antitumor activities has also been suggested. The aim of the current study was to evaluate their in vitro effects on some human transformed cell lines. Materials and Methods: Cytotoxicity of the four drugs was tested in MCF-7, HeLa and HepG2 cells by the neutral red assay method and also the effect of rosuvastatine and doxazosin against Ehrlich Ascities Carcinoma Cells (EACC) by trypan blue assay. Results: Rosuvastatine exerted the greatest cytotoxic effect against HepG2 cells with an IC 50 value of 58.7±69.3; in contrast doxazosin showed least activity with IC 50 =104.4 ±115.7. Repaglinide inhibited the growth of both HepG2 and HeLa cells with IC 50 values of 87.6±117.5 and 89.3±119.5, respectively. Oxcarbazepine showed a potent cytotoxicity against both HeLa (IC 50 =19.4±43.9) and MCF7 cancer cells ((IC 50 =22±35.7).On the other hand the growth of EACC was completely inhibited by doxazosine (100% inhibition) while rosuvastatine had weak inhibitory activity (11.6%). Conclusions: The four tested drugs may have cytotoxic effects against hepatic, breast and cervical carcinoma cells; also doxazosine may inhibit the growth of endometrial cancer cells. Further investigations in animals are needed to confirm these results.
Bioorganic & Medicinal Chemistry Letters
Bioorganic & Medicinal Chemistry Letters, 2001
Bioorganic & Medicinal Chemistry Letters publishes research communications of outstanding significance and timeliness on topics at the interface of chemistry and biology, together with invited concise review articles. The journal publishes reports of experimental results in medicinal chemistry, chemical biology and drug discovery and design, emphasizing new and emerging advances and concepts in these fields. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. The journal continues to be a major forum for the first publication of new chemical entities prior to them entering clinical trials. The Journal welcomes papers on: the medicinal chemistry and associated biology (including target identification and validation) of established or new disease targets the reporting of the discovery, design or optimization of potent new compounds or biological agents the analysis and discussion of structure-activity relationships and pharmacological issues relevant to drug design and action using in vitro and in vivo models, including the use of computational techniques when closely linked to experimental data the reporting of "first-in-class" new therapeutic compounds the chemical biology or bioorganic/bioinorganic chemistry that significantly advances knowledge of a biological mechanism methodological advances that are chemistry-based and which significantly impact on medicine or biology the preparation and examination of biotherapeutics for the treatment of pathophysiological disease states the development of materials for specific therapeutic targeting Manuscripts on phytochemistry, theoretical molecular dynamics and exclusively computational papers are out of scope. All manuscripts will be rigorously peer-reviewed by independent experts following an initial assessment by the Editors. Please note that BMCL is not suitable for straightforward reports of incremental advances. Above all the presentation of a rational basis and a sound underlying hypothesis for the work is of particular importance, whatever its exact field.
RENOPROTECTIVE POTENTIAL OF FLAVONOIDS-RICH AGAINST DOXORUBICIN-INDUCED IN ANIMAL MODELS: A REVIEW
International Journal of Applied Pharmaceutics, 2024
Cancer significantly impacts human health, affecting one in five people during their lifetime. While chemotherapeutic agents like doxorubicin are crucial in treating various cancers, they are also associated with severe side effects, including nephrotoxicity. This review examines the renoprotective potential of flavonoids against doxorubicin-induced renal damage in animal models. Doxorubicin works by intercalating Deoxyribo Nucleic Acid (DNA) and making Reactive Oxygen Species (ROS), which cause apoptosis and the death of cells. A thorough literature analysis was done to collect relevant papers on the impact of flavonoid-rich therapies as renoprotective agents against doxorubicin-induced nephrotoxicity. Databases such as Google Scholar, Scopus, PubMed, Springer, Wiley Online Library, and ScienceDirect were searched using keywords including "flavonoids, doxorubicin, renoprotective, nephrotoxicity, and animal model," focusing on publications from 2014 to 2024. Flavonoids are diverse polyphenolic compounds in many plants with significant pharmacological properties such as antioxidant, anti-inflammatory, and anticancer effects. This review highlights the renoprotective potential of flavonoids like quercetin, rutin, kaempferol, morin, luteolin, apigenin, hesperidin, naringenin, diosmin, and anthocyanins. These compounds reduce renal toxicity through mechanisms that decrease ROS, lipid peroxidation, mitochondrial permeability, and apoptosis.
Medical science monitor : international medical journal of experimental and clinical research, 2002
Reactive oxygen species are known to be potentially dangerous, but are also needed for signal-transduction pathways. Tumor cells have relatively low amounts of superoxide dismutase (SOD), which quenches superoxide anion (O2(-*)), and as a result of a higher level of aerobic metabolism, higher concentrations of O2(-*) , compared to normal cells. But this may not be true of all tumor cells. Some tumor cells have relatively higher amounts of vitamin E, a potent anti-oxidant, and a higher level of anaerobic metabolism, resulting in a balance that is tilted more towards higher anti-oxidant capacity. In both instances of higher aerobic and anaerobic metabolism methods designed to augment free radical generation in tumor cells can cause their death. It is suggested that free radicals and lipid peroxides suppress the expression of Bcl-2, activate caspases and shorten telomere, and thus inducing apoptosis of tumor cells. Ionizing radiation, anthracyclines, bleomycin and cytokines produce fre...
EXPERIMENTAL AND THERAPEUTIC MEDICINE
Ineffectiveness of cancer therapy may originate in the incompatibility of the treatment with various mutations in the cancer cells. Finding novel anticancer treatments that work efficiently for varying types of cancer cells remains challenging. Previous studies have identified that compounds in sea cucumbers are capable of inhibiting the growth of cancer cells and inducing apoptosis. However, information on the underlying mechanisms controlling cancer cell growth at a molecular level remains limited. The current study analyzed the potential of colochiroside A, ds-echinoside A, philinopside E, sphingosine and stichoposide C as inhibitors for anticancer target proteins, including mouse double minute 2 homolog (MDM2) and C-X-C chemokine receptor type 4 (CXCR4). Inhibition of MDM2 triggers apoptosis through regulation of tumor protein 53 and CXCR4 inhibition may prevent cancer cell proliferation and growth by affecting the Janus kinase 2/3 signal transducer and activator of transcription signaling pathway and protein tyrosine kinase 2. The results of a binding affinity analysis using molecular docking revealed that philinopside E and ds-echinoside A may inhibit MDM2 and CXCR4. The data suggested that these active compounds may be promising inhibitors of cell growth by binding to two targets simultaneously. Furthermore, stichoposide C and colochiroside A were predicted to inhibit CXCR4. Additional research is needed to validate the in vitro activity of the aforementioned compounds.
Croatian Medical Journal, 2014
Aim To use the antioxidant compounds (sodium selenite, selenomethionine, D-pantethine) for modulation of cytotoxic effect of doxorubicin and cisplatin toward wild type and drug-resistant mutants of several human tumor cells. Similar treatments were applied in vivo toward adult male Wistar rats. Methods Human tumor cells of different lines (HCT-116, Jurkat and HL-60) with various mechanisms of drug-resistance were treated with doxorubicin or cisplatin, alone or in combination with sodium selenite, selenomethionine, or D-pantethine. Cell viability, induction of apoptosis, and production of O 2 radicals were measured. Activity of redox potential modulating enzymes was measured in the liver and blood plasma of adult male Wistar rats subjected to similar treatments. Results All antioxidants used in physiologically harmless concentration inhibited cytotoxic action of doxorubicin toward tumor cells sensitive to chemotherapy treatment by 15%-30%, and slightly enhanced cytotoxic effect of this medicine toward drug-resistant malignant cells. At the same time, there was no significant effect of these antioxidants on cisplatin action. Such effects were accompanied by a complete inhibition of production of superoxide radicals induced by doxorubicin. The results of in vivo study in adult male Wistar rats were in agreement with the results of in vitro study of human tumor cells. Conclusion Protective effect of specific antioxidant agents during cytotoxic action of doxorubicin was demonstrated in vitro in drug-sensitive human tumor cells and in adult male Wistar rats, while there was no protective effect in drug-resistant sub-lines of these tumor cells during action of doxorubicin and cisplatin.