Role of reactive oxygen species in cis-dichlorodiammineplatinum-induced cytotoxicity on bladder cancer cells

Miyajima, Akira; Nakashima, Jun; Yoshioka, Kunihiko; Tachibana, Masaaki; Tazaki, Hiroshi; Murai, Masaru

doi:10.1038/bjc.1997.363

Cited by 162 publications

(112 citation statements)

References 25 publications

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“…These findings are in agreement with other findings demonstrating that ROS is closely associated with cisplatin-induced apoptosis. [6][7][8][9] Our data also showed that cisplatin treatment induced the loss of MMP. Likewise, overexpression of Bcl-2 blocked cisplatininduced MMP loss and protected HN4 cells from both caspase-dependent and caspase-independent apoptosis induced by cisplatin treatment.…”

Section: Discussionsupporting

confidence: 60%

“…Indeed, increased generation of ROS is closely associated with cisplatin-induced apoptosis. [6][7][8][9] ROS have been reported to activate the mitochondrial permeability transition, resulting in mitochondrial membrane potential (MMP) loss. 10,11 Loss of the MMP is considered to be involved in the apoptotic process induced by chemotherapeutic drugs [12][13][14] and can induce the release of potentially apoptogenic proteins such as cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) from the intermembrane space.…”

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen species‐dependent EndoG release mediates cisplatin‐induced caspase‐independent apoptosis in human head and neck squamous carcinoma cells

Kim

Lee

Jeong

et al. 2007

Intl Journal of Cancer

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Cisplatin is a chemotherapeutic agent that is widely used to treat cancers such as head and neck squamous cell carcinoma (HNSCC). Previously, we have reported that cisplatin induced an early caspase-dependent apoptosis (8 hr) in a HNSCC cell, HN4. In this study, we examined a late caspase-independent apoptosis as well as an early caspase-dependent apoptosis in cisplatintreated HN4 cells. While z-VAD-fmk, a pan-caspase inhibitor, blocked the caspase activities and protected cells from the early apoptosis, it did not provide protection against delayed apoptosis occurring after extended exposure (16 hr) to cisplatin, suggesting that the delayed apoptotic response in the presence of z-VAD-fmk was caspase-independent. Cisplatin treatment induced reactive oxygen species (ROS) generation, loss of the mitochondrial membrane potential (MMP) and nuclear translocation of endonuclease G (EndoG). Small interfering RNA mediated-knockdown of EndoG significantly protected cells from the delayed apoptosis induced by cisplatin in the presence of z-VAD-fmk. Overexpression of Bcl-2 in HN4 cells prevented loss of MMP, nuclear translocation of EndoG and protected cells from the delayed apoptosis induced by cisplatin in the presence of z-VAD-fmk. Pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, prevented both ROS generation, loss of the MMP and nuclear translocation of EndoG. Together, our data indicate that cisplatin treatment induced ROS-mediated loss of the MMP, and, then, the nuclear translocation of EndoG, which played a crucial role in caspase-independent apoptosis of HN4 cells in the presence of z-VAD-fmk. This is the first report about the involvement of EndoG in cisplatin-induced caspase-independent apoptosis of cells. ' 2007 Wiley-Liss, Inc.

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Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Reactive oxygen species‐dependent EndoG release mediates cisplatin‐induced caspase‐independent apoptosis in human head and neck squamous carcinoma cells

Kim

Lee

Jeong

et al. 2007

Intl Journal of Cancer

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“…Exposure of cells to CDDP or to other anticancer agents can induce the production reactive oxygen species (ROS) (Benhar et al, 2001;Miyajima et al, 1997;Simizu et al, 1998). In our previous study we demonstrated that CDDP-induced activation of JNK and p38 MAPKs was dependent on the production of ROS (Benhar et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Cisplatin-induced activation of the EGF receptor

2002

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Cisplatin (CDDP) is an efficient DNA-damaging antitumor agent employed for the treatment of various human cancers. CDDP activates nuclear as well as cytoplasmatic signaling pathways involved in regulation of the cell cycle, damage repair and programmed cell death. Here we report that CDDP also activates a membrane-integrated protein, the epidermal growth factor receptor (EGFR). We show that EGFR is activated in response to CDDP in various types of cells that overexpress the receptor, including transformed human glioma cells and human breast tumor cells. CDDP-induced EGFR activation requires its kinase activity, as it can be blocked by an EGFR kinase inhibitor or by expression of a kinase dead receptor. We also show that CDDP-induced EGFR activation is independent of receptor ligand. CDDP induces the activation of c-Src, and EGFR activation is blocked by Src-family inhibitor PP1, suggesting that Src kinases mediate CDDP-induced EGFR activation. We propose that EGFR activation in response to CDDP is a survival response, since inhibition of EGFR activation enhances CDDP-induced death. These findings show that signals generated by DNA damage can modulate EGFR activity, and argue that interfering with CDDP-induced EGFR activation in tumor cells might be a useful approach to sensitize these cells to genotoxic agents.

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“…Cisplatininduced cytotoxicity has been associated with the generation of ROS in cells. (33,34) The cisplatin-induced accumulation of ROS was found to be markedly suppressed in the inherently cisplatin-resistant HT-29 colon adenocarcinoma cell line. (35,36) In addition, the antitumor activity of HDAC inhibitors has also been associated with their ability to induce the intracellular accumulation of ROS.…”

Section: Hdac Inhibitors Potentiate Induction Of Apoptosis By Cisplatinmentioning

confidence: 99%

Histone deacetylase inhibitors enhance the chemosensitivity of tumor cells with cross‐resistance to a wide range of DNA‐damaging drugs

et al. 2008

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Cancer is a disease of genetic defects such as gene mutations and deletions as well as chromosomal abnormalities, which together result in the gain of function or hyperactivation of oncogenes, or the loss of function of tumor suppressor genes. Recent evidence indicates, however, that changes in gene expression attributable to epigenetic alterations also contribute to the onset and progression of cancer.(1,2) Remodeling of chromatin between relatively open and closed states plays a key role in the epigenetic regulation of gene expression. Such remodeling is induced by modification of the structure of nucleosomes, which consist of approximately two turns of the DNA helix wound around a histone octamer. Regulation of nucleosome structure is mediated in part by modification of the amino-terminal tail of histones.(3) Acetylation of histones (in particular, histones H3 and H4), which is determined by the opposing activities of histone acetyltransferases (HAT) and histone deacetylases (HDAC), is central to the regulation of gene expression through chromatin modification.(4) HAT transfer acetyl groups to lysine residues in the amino-terminal tail of histones, resulting in local expansion of chromatin and increased accessibility of the DNA to regulatory proteins, whereas HDAC catalyze the removal of acetyl groups, leading to chromatin condensation and transcriptional repression. (6 -8) Reduced levels of histone acetylation as a result of aberrant HDAC activity have thus been detected in several human tumors and appear to trigger repression of tumor suppressor genes and to contribute to tumor onset and progression. (9) Specific inhibition of HDAC activity has therefore emerged as a potential strategy to reverse epigenetic changes associated with cancer. Several small-molecule HDAC inhibitors have recently been shown to exhibit potent and specific anticancer activity in preclinical studies. (10)(11)(12)(13)(14) Multiple mechanisms have been proposed for the anticancer activity of HDAC inhibitors, which include the enhanced acetylation of core histones and consequent increased accessibility of genomic DNA to transcriptional complexes, resulting in the induction of tumor suppressor genes.(10,15) The hyper-acetylation of histones induced by the HDAC inhibitor trichostatin A (TSA) has been shown to increase chromatin accessibility by measurement of the size-dependent nuclear distribution of microinjected fluorescein isothiocyanate-dextran conjugates with the use of image-correlation spectroscopy.(16) Such an HDAC inhibitorinduced relaxation of chromatin structure would be expected to increase chromatin accessibility not only to transcription factors but also to therapeutic agents that target genomic DNA. Consistent with this notion, HDAC inhibitors have been shown to sensitize tumor cells to the induction of cell death by ionizing radiation, (17,18) ultraviolet (UV) radiation, (19) and several DNA-damaging drugs. (20,21) The molecular mechanisms of such effects have remained largely unknown.Anticancer drugs that induce DNA dam...

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Role of reactive oxygen species in cis-dichlorodiammineplatinum-induced cytotoxicity on bladder cancer cells

Cited by 162 publications

References 25 publications

Reactive oxygen species‐dependent EndoG release mediates cisplatin‐induced caspase‐independent apoptosis in human head and neck squamous carcinoma cells

Reactive oxygen species‐dependent EndoG release mediates cisplatin‐induced caspase‐independent apoptosis in human head and neck squamous carcinoma cells

Cisplatin-induced activation of the EGF receptor

Histone deacetylase inhibitors enhance the chemosensitivity of tumor cells with cross‐resistance to a wide range of DNA‐damaging drugs

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