The role of caspase family protease, caspase-3 on cisplatin-induced apoptosis in cisplatin-resistant A431 cell line

Mese, Hiroshi; Sasaki, Akira; Nakayama, Shuko; Alcalde, Rafael; Matsumura, Tomohiro

doi:10.1007/s002800000145

Cited by 29 publications

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“…Although cisplatin-induced apoptosis occurs through caspasedependent and caspase-independent mechanisms (Gonzalez et al, 2001), caspase-dependent apoptosis has been reported for the A431 cell line (Mese et al, 2000;Sawada et al, 2003). We examined the involvement of caspases during Titanocene Y-induced apoptosis in A431 cells.…”

Section: Discussionmentioning

confidence: 99%

Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

et al. 2007

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Titanocene compounds are a novel series of agents that exhibit cytotoxic effects in a variety of human cancer cells in vitro and in vivo. In this study, the antiproliferative activity of two titanocenes (Titanocenes X and Y) was evaluated in human epidermoid cancer cells in vitro. Titanocenes X and Y induce apoptotic cell death in epidermoid cancer cells, with IC50 values that are comparable to cisplatin. Characterisation of the cell death pathway induced by titanocene compounds in A431 cells revealed that apoptosis is preceded by cell cycle arrest and the inhibition of cell proliferation. The induction of apoptosis is dependent on the activation of caspase-3 and -7 but not caspase-8. Furthermore, the antitumour activity of Titanocene Y was tested in an A431 xenograft model of epidermoid cancer. Results indicate that Titanocene Y significantly reduced the growth of A431 xenografts with an antitumour effect similar to cisplatin. These results suggest that titanocenes represent a novel series of promising antitumour agents.

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Section: Discussionmentioning

confidence: 99%

Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

et al. 2007

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“…However, cisplatin directly binds DNA by forming intra-and interstrand crosslinks which cause the DNA to unwind and bind other proteins, thus preventing DNA repair. Like etoposide, cisplatin-induced apoptosis has been found to invoke a caspase-3 mediated pathway (Mese et al, 2000). The 293 HEK stable cell lines were exposed to 10 lg/mL cisplatin with subsequent data analysis at 24 h intervals.…”

Section: Chemical Exposure Of Stably Transfected 293 Hek Cellsmentioning

confidence: 99%

Inhibiting apoptosis in mammalian cell culture using the caspase inhibitor XIAP and deletion mutants

Sauerwald

Betenbaugh

Oyler

2002

Biotech & Bioengineering

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Lower yields and poorer quality of biopharmaceutical products result from cell death in bioreactors. Such cell death may occur from necrosis but is more commonly associated with apoptosis. During the process of programmed cell death or apoptosis, caspases become activated and cause a cascade of events that eventually destroy the cell. XIAP is the most potent caspase inhibitor encoded in the mammalian genome. The effectiveness of XIAP and its deletion mutants was examined in two cell lines commonly utilized in commercial bioreactors: Chinese hamster ovary (CHO) and 293 human embryonic kidney (293 HEK) cells. CHO cells undergo apoptosis as a result of various insults, including Sindbis virus infection and serum deprivation. In this study, we demonstrate that 293 HEK cells undergo apoptosis during Sindbis virus infection and exposure to the toxins, etoposide and cisplatin. Two deletion mutants of XIAP were created; one containing three tandem baculovirus iap repeat (BIR) domains and the other containing only the C-terminal RING domain, lacking the BIRs. Viability studies were performed for cells expressing each mutant and the wild-type protein on transiently transfected cells, as stable pools, or as stable clonal cell populations after induction of apoptosis by serum deprivation, Sindbis virus infection, etoposide, and cisplatin treatment. Expression of the wild-type XIAP inhibited apoptosis significantly; however, the XIAP mutant containing the three BIRs provided equivalent or improved levels of apoptosis inhibition in all cases. Expression of the RING domain offered no protection and was pro-apoptotic in transient expression experiments. With the aid of an N-terminal YFP fusion to each protein, distribution within the cell was visualized, and the wild-type and mutants showed differing intracellular accumulation patterns. While the wild-type XIAP protein accumulated primarily in aggregates in the cytosol, the RING mutant was enriched in the nucleus. In contrast, the deletion mutant containing the three BIRs was distributed evenly throughout the cytosol. Thus, protein engineering of the XIAP protein can be used to alter the intracellular distribution pattern and improve the ability of this caspase inhibitor to protect against apoptosis for two mammalian cell lines.

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“…Amphotericin B-induced apoptosis as noted by the nucleosome ELISA was apparently not dependent on caspase-3 activation. Caspase-3 activity measurements of cisplatin-induced apoptosis 11 were valuable as the cisplatin effect on nucleosome fragmentation was less pronounced.…”

Section: Discussionmentioning

confidence: 99%

“…Like most chemotherapeutic agents, cisplatin and carboplatin exert their action by inducing apoptosis, 9,10 probably mediated through caspase-3 activation. [11][12][13] To explore if enhanced potassium efflux could affect cisplatin and/or carboplatin induction of apoptosis and cytotoxicity we used amphotericin B as K ϩ ionophore. Amphotericin B is a polyene anti-fungal antibiotic known to potentiate cisplatin cytotoxicity in normal and cisplatinresistant cells, 14,15 by inducing cell membrane pores leading to potassium efflux.…”

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confidence: 99%

Cisplatin-induced apoptosis of mesothelioma cells is affected by potassium ion flux modulator amphotericin B and bumetanide

2001

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Key words: amphotericin B; apoptosis; bumetanide; carboplatin; cisplatin; cytotoxicity; potassium channelsThe efflux of ions, primarily potassium ions, plays an important role during the induction of apoptosis. Apoptosis with ensuing reduction in cell volume is enhanced under conditions when the intracellular K ϩ concentration is diminished, and only shrunken cells with reduced K ϩ exhibit DNA fragmentation and elevation of caspase-3-like activity-hallmarks of apoptosis. 1 Increased inward pumping of potassium ions counteracts apoptosis. 2 The major transport system accumulating ions in shrunken cells is NaϪ -cotransport. 3-5 Modulation of K ϩ efflux or influx rates could thus decrease or increase apoptosis due to the nature of the disruption of cellular potassium homeostasis. Because the mechanism by which several of the chemotherapeutic anti-cancer agents exert their effect involve induction of apoptosis, the tumoricidal effects could subsequently be altered. 6 -8 The platinum-based drug cisplatin (cis-diammine-dichloroplatinum) and its less toxic analogue carboplatin (cis-diammine-1,1-cyclobutanedicarboxyplatinum) are widely used in cancer treatment, alone or in combination with other anti-tumor drugs, against several solid tumors. Like most chemotherapeutic agents, cisplatin and carboplatin exert their action by inducing apoptosis, 9,10 probably mediated through caspase-3 activation. [11][12][13] To explore if enhanced potassium efflux could affect cisplatin and/or carboplatin induction of apoptosis and cytotoxicity we used amphotericin B as K ϩ ionophore. Amphotericin B is a polyene anti-fungal antibiotic known to potentiate cisplatin cytotoxicity in normal and cisplatinresistant cells, 14,15 by inducing cell membrane pores leading to potassium efflux. 16 To inhibit NaϪ -cotransport-dependent potassium influx, we used the clinically used diuretic drug bumetanide, a specific NaϪ -cotransport blocker. The effects of K ϩ flux modulators on cisplatin-and carboplatin-induced apoptosis and cytotoxicity were studied on a pulmonary mesothelioma cell line (P31), which to a large extent expresses NaϪ -cotransport activity. 17 MATERIAL AND METHODS Cell cultureHuman pulmonary mesothelioma cells (P31) were grown as monolayer culture in Eagle's minimal essential medium (MEM) in Earl's saline supplemented with 10% fetal calf serum and 200 mol/L L-glutamine. Analysis of DNA integrityEndonuclease-mediated nucleosome excision, observable as a DNA ladder in agarose gels was first used as a qualitative screening assay for apoptosis. Following a 6-hr incubation with 0, 0.05, 0.5, 5 or 50 mg/L cisplatin, P31 cells that had become nonadherent were suspended in phosphate-buffered bovine serum albumin (pBSA), centrifuged (3,000 g) and then resuspended in digestion buffer (100 mmol/L sodium chloride, 10 mmol/L TRISHCl pH 8, 0.5% sodium dodecyl sulfate and 0.1 mmol/L proteinase K), incubated for 12 hr at 50°C, followed by treatment with DNAse-free RNAse (0.5 mg/ml) for 1 hr. Loading buffer was added to each sample before loading on...

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The role of caspase family protease, caspase-3 on cisplatin-induced apoptosis in cisplatin-resistant A431 cell line

Abstract: These findings suggest that caspase-3 may mediate apoptosis induced by CDDP, and its induction could represent a novel approach to the effective treatment of malignant tumors.

Cited by 29 publications

References 0 publications

Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

Inhibiting apoptosis in mammalian cell culture using the caspase inhibitor XIAP and deletion mutants

Cisplatin-induced apoptosis of mesothelioma cells is affected by potassium ion flux modulator amphotericin B and bumetanide

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