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Cancer Cell Death (cancer + cell_death)
Selected AbstractsAccumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo,INTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Jérôme Alexandre Abstract Intracellular events following paclitaxel binding to microtubules that lead to cell death remain poorly understood. Because reactive oxygen species (ROS) are involved in the cytotoxicity of anticancer agents acting through independent molecular targets, we explored the role of ROS in paclitaxel cytotoxicity. Within 15 min after in vitro exposure of A549 human lung cancer cells to paclitaxel, a concentration-dependent intracellular increase in O°2, and H2O2 levels was detected by spectrofluorometry. Addition of N -acetylcysteine (NAC) or glutathione, two H2O2 scavenger, induced a 4-fold increase in paclitaxel IC50. Delaying NAC co-incubation by 4 hr, resulted in a 3-fold reduction in cell protection. The glutathione synthesis inhibitor, buthionine sulfoximine significantly increased paclitaxel cytotoxicity and H2O2 accumulation, but did not modify O°2, levels. Co-incubation with diphenylene iodonium suggested that paclitaxel induced-O°2, production was in part associated with increased activity of cytoplasmic NADPH oxidase. Concomitant treatment with inhibitors of caspases 3 and 8 increased cell survival but did not prevent the early accumulation of H2O2. To evaluate the role of ROS in paclitaxel antitumoral activity, mice were injected with LLC1 lung cancer cells and treated with paclitaxel i.p. and/or NAC. The antitumoral activity of paclitaxel in mice was abolished by NAC. In conclusion, the accumulation of H2O2 is an early and crucial step for paclitaxel-induced cancer cell death before the commitment of the cells into apoptosis. These results suggest that ROS participate in vitro and in vivo to paclitaxel cytotoxicity. © 2006 Wiley-Liss, Inc. [source] Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 7 2010Chi-Cheng Lu Abstract Anthraquinone compounds have been shown to induce apoptosis in different cancer cell types. Effects of chrysophanol, an anthraquinone compound, on cancer cell death have not been well studied. The goal of this study was to examine if chrysophanol had cytotoxic effects and if such effects involved apoptosis or necrosis in J5 human liver cancer cells. Chrysophanol induced necrosis in J5 cells in a dose- and time-dependent manner. Non-apoptotic cell death was induced by chrysophanol in J5 cells and was characterized by caspase independence, delayed externalization of phosphatidylserine and plasma membrane disruption. Blockage of apoptotic induction by a general caspase inhibitor (z-VAD-fmk) failed to protect cells against chrysophanol-induced cell death. The levels of reactive oxygen species production and loss of mitochondrial membrane potential (,,m) were also determined to assess the effects of chrysophanol. However, reductions in adenosine triphosphate levels and increases in lactate dehydrogenase activity indicated that chrysophanol stimulated necrotic cell death. In summary, human liver cancer cells treated with chrysophanol exhibited a cellular pattern associated with necrosis and not apoptosis. [source] Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas,APMIS, Issue 3 2003NAM JIN YOO Second mitochondria-derived activator of caspases (Smac/DIABLO) is released from mitochondria into the cytosol during apoptosis, promoting caspase activation by neutralizing the inhibition of inhibitor of apoptosis proteins (IAPs) on caspases. Alteration of apoptosis is essential for cancer development, and cancer cell death by radiation and chemotherapy is largely dependent upon apoptosis. In this study, archival tissues of 100 carcinomas and 50 sarcomas from various origins were analyzed by immunohistochemistry for the expression of Smac/DIABLO. Smac/DIABLO immunoreactivity was seen in 62 of 100 (62%) carcinomas, including 42 of 60 stomach carcinomas, 7 of 10 colorectal carcinomas, 4 of 10 lung carcinomas, 7 of 10 ovarian carcinomas, and 2 of 10 prostate carcinomas. Smac/DIABLO is expressed in 11 of 50 (22%) sarcomas, including 2 of 8 malignant schwannomas, 5 of 11 rhabdomyosarcomas, 2 of 7 malignant fibrous histiocytomas, 1 of 6 leiomyosarcomas, 0 of 8 angiosarcomas, 0 of 8 liposarcomas, and 1 of 2 Ewing's sarcomas. These data demonstrated that Smac/DIABLO expression levels vary depending on the individual cancer types. Furthermore, the present study showed that many human cancers do not express Smac/DIABLO, and suggest that lack of Smac/DIABLO expression in the cancer cells may inhibit apoptosis, thereby promoting their survival. [source] (,)-Epigallocatechin-3-gallate induces Du145 prostate cancer cell death via downregulation of inhibitor of DNA binding 2, a dominant negative helix-loop-helix proteinCANCER SCIENCE, Issue 3 2010Katherine L. Luo (Cancer Sci 2010; 101: 707,712) (,)-Epigallocatechin-3-gallate (EGCG) is one of the major polyphenol components in green tea. It effectively induces apoptosis in prostate cancer cells. The anticancer effect of this reagent is appealing because it is a natural component of a popular daily beverage that has proven harmless for thousands of years, making it a good candidate chemopreventive agent. EGCG suppresses cell growth and causes cell death, but the mechanisms are not well characterized, especially in androgen-independent prostate cancer cells. In the present study, using Affymetrix genechip Hu133 2.0, we analyzed the gene expression patterns of the androgen-independent prostate cancer cell line Du145, treated with or without EGCG, and found 40 genes whose expression levels were altered (>twofold, either upregulated or downregulated, P < 0.01) upon treatment with EGCG. These gene products are involved in the functions of transcription, RNA processing, protein folding, phosphorylation, protein degradation, cell motility, and ion transport. Among them, inhibitor of DNA binding 2 (ID2), known as a dominant anti-retinoblastoma (Rb) helix-loop-helix protein, was found to be downregulated fourfold by EGCG treatment. Forced expression of ID2 in Du145 cells reduced apoptosis and increased cell survival in the presence of EGCG, and knockdown ID2 expression in Du145 cells using a morpholino oligonucleotide specific for ID2 mimicked the apoptosis effect generated by EGCG treatment, although it was milder. To our knowledge, this is the first report indicating that ID2 is one of the critical factors in the signaling pathway of Du145 cell death induced by EGCG. [source] | ||||||||||