Cleavage of Bax-α and Bcl-xL during carboplatin-mediated apoptosis in squamous cell carcinoma cell line

Itoh, Mizue; Chiba, Hiroshige; Noutomi, T.; Takada, Eiko; Mizuguchi, Junichiro

doi:10.1016/s1368-8375(00)00010-5

Cited by 30 publications

(23 citation statements)

References 39 publications

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“…Apoptosis can be induced in LCLs by pharmacologic agents, such as the chemotherapeutic drug carboplatin (20,32). Apoptosis induced by carboplatin is at least partially caspase-9-dependent (33), although caspase-8 may also be involved (34). We observed an association between rs514182 and sensitivity to carboplatin in the same LCLs (Fig.…”

Section: Resultsmentioning

confidence: 64%

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Ko¹,

Gamazon

Shukla³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Genome-wide association studies can identify common differences that contribute to human phenotypic diversity and disease. When genome-wide association studies are combined with approaches that test how variants alter physiology, biological insights can emerge. Here, we used such an approach to reveal regulation of cell death by the methionine salvage pathway. A common SNP associated with reduced expression of a putative methionine salvage pathway dehydratase, apoptotic protease activating factor 1 (APAF1)-interacting protein (APIP), was associated with increased caspase-1-mediated cell death in response to Salmonella. The role of APIP in methionine salvage was confirmed by growth assays with methionine-deficient media and quantitation of the methionine salvage substrate, 5′-methylthioadenosine. Reducing expression of APIP or exogenous addition of 5′-methylthioadenosine increased Salmonellae-induced cell death. Consistent with APIP originally being identified as an inhibitor of caspase-9-dependent apoptosis, the same allele was also associated with increased sensitivity to the chemotherapeutic agent carboplatin. Our results show that common human variation affecting expression of a single gene can alter susceptibility to two distinct cell death programs. Furthermore, the same allele that promotes cell death is associated with improved survival of individuals with systemic inflammatory response syndrome, suggesting a possible evolutionary pressure that may explain the geographic pattern observed for the frequency of this SNP. Our study shows that in vitro association screens of disease-related traits can not only reveal human genetic differences that contribute to disease but also provide unexpected insights into cell biology.HapMap | lymphoblastoid | pyroptosis | quantitative trait | polygenic adaptation

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Section: Resultsmentioning

confidence: 64%

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Ko¹,

Gamazon

Shukla³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…[19][20][21] Following treatment with the DNAdamaging agent, camptothecin, HL-60 cells undergo apoptosis in association with Bax cleavage into a p18 product ( Figure 1A). Similar results are observed when K-562, U-937, and A-549 cells are treated with cisplatin or etoposide ( Figure 1C-D), ruling out a nonspecific or cell type-specific effect for Bax cleavage.…”

Section: Cleavage Of Bax To P18 Bax Is Closely Associated With Apoptomentioning

confidence: 99%

“…Proteolytic cleavage of Bax was reported to occur in tumor cells treated with various chemotherapeutic agents that activate the intrinsic apoptotic pathway. [19][20][21] Bax was shown to be cleaved at aspartate 33 (Asp33) by calpain to yield a p18 Bax product. 22,23 While p18 Bax formation is associated with apoptosis, whether p18 Bax contributes to mitochondrial dysfunction or is merely a proteolytic by-product is not clear.…”

Section: Introductionmentioning

confidence: 99%

Cleavage of Bax to p18 Bax accelerates stress-induced apoptosis, and a cathepsin-like protease may rapidly degrade p18 Bax

Cao

Deng

May

2003

Blood

103

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“…The anti-tumor activity of carboplatin is similar to cisplatin, including induction of apoptosis mediated by activation of caspases. 13 In this study, amphotericin B (with or without bumetanide) had an effect on cisplatin cytotoxicity in the colony-forming assay, but the effect was more enhanced in the fluorometric cytotoxicity assay. The exposure time (1 and 72 hr, respectively) could perhaps explain the difference.…”

Section: Discussionmentioning

confidence: 57%

“…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.…”

mentioning

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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Cleavage of Bax-α and Bcl-xL during carboplatin-mediated apoptosis in squamous cell carcinoma cell line

Cited by 30 publications

References 39 publications

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Cleavage of Bax to p18 Bax accelerates stress-induced apoptosis, and a cathepsin-like protease may rapidly degrade p18 Bax

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

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