Analysis of the inhibition of mammalian thioredoxin, thioredoxin reductase, and glutaredoxin by cis -diamminedichloroplatinum (II) and its major metabolite, the glutathione-platinum complex

Arnér, Elias S.J.; Nakamura, Hajime; Sasada, Tetsuro; Yodoi, Junji; Holmgren, Arne; Spyrou, Giannis

doi:10.1016/s0891-5849(01)00698-0

Cited by 157 publications

(108 citation statements)

References 52 publications

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“…In addition, the pharmacologic or genetic modulation of thioredoxin or glutathione S-transferase-k has been reported to effectively increase the intracellular ROS level (26,45,46). Previously, we also reported that the combinational use of CDDP and dicoumarol, an enzymatic inhibitor of antioxidant enzyme NADPH quinone oxidoreductase 1, accelerated CDDP-induced apoptosis via the activation of JNK (12), but it was effective only in bladder cancer cells with WT p53.…”

Section: Discussionmentioning

confidence: 93%

Sensitizing Effect of Galectin-7 in Urothelial Cancer to Cisplatin through the Accumulation of Intracellular Reactive Oxygen Species

et al. 2007

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To improve chemotherapeutic efficacy in urothelial cancer, it is important to identify predictive markers for chemosensitivity as well as possible molecules accelerating cell killing mechanisms. In this study, we assessed the possibility of galectin-7 to accelerate cis -diamminedichloroplatinum (CDDP)-induced cell killing in vitro and also to predict chemosensitivity against CDDP in urothelial cancer patients. The expression of galectin-7 was analyzed in five bladder cancer cell lines with different p53 status after treatment with CDDP. The roles of galectin-7 in chemosensitivity against CDDP were analyzed by transfection of the galectin-7 gene into several of these cell lines. Furthermore, the relationship between the expression of galectin-7 and the response to neoadjuvant chemotherapy was analyzed in 17 human bladder cancer specimens. Exposure to CDDP induced galectin-7 in cell lines with wild-type p53 but not in those with mutated p53. When the galectin-7 gene was transfected into cell lines with mutated p53, the sensitivity to CDDP increased compared with control transfectants. In addition, galectin-7-transfected cells exhibited more accumulation of intracellular reactive oxygen species and activation of c-Jun NH 2 -terminal kinase (JNK) and Bax than control transfectants. SP600125, an inhibitor of JNK, or antioxidant N-acetyl-L-cysteine inhibited the enhancement of chemosensitivity against CDDP by galectin-7 transfection. In clinical samples, the expression levels of galectin-7 were significantly lower in urothelial carcinomas compared with normal urothelium. When chemosensitivity was tested, its expression levels were higher in the chemosensitive group than in the chemoresistant group. Galectin-7 is a candidate for a predictive marker of chemosensitivity against CDDP, and the targeted expression of galectin-7 might overcome the chemoresistance of urothelial cancer. [Cancer Res 2007;67(3):1212-20]

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Section: Discussionmentioning

confidence: 93%

Sensitizing Effect of Galectin-7 in Urothelial Cancer to Cisplatin through the Accumulation of Intracellular Reactive Oxygen Species

et al. 2007

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“…By restoring TRX expression, U0126 inhibited ROS accumulation, and protected against necrosis. Cisplatin lowered TRX levels in the E47 cells (Fig 10), and human TRX was shown to protect against cisplatin cytotoxicity (46,47). Thus, inhibition of ERK by U0126 in E47 cells caused dual effects: inhibition of ERK protected against necrosis, probably via TRX's antioxidant action (other antioxidants also protected against the cisplatin plus BSO induced necrosis); on the other hand, inhibition of ERK restored activities of caspases and switched necrosis to apoptosis, probably via maintaining the redox state of cells by TRX.…”

Section: Discussionmentioning

confidence: 95%

The mode of cisplatin-induced cell death in CYP2E1-overexpressing HepG2 cells: Modulation by ERK, ROS, glutathione, and thioredoxin

Cederbaum

2007

Free Radical Biology and Medicine

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In a previous study, E47 HepG2 cells that overexpress human CYP2E1 were shown to be more sensitive to cisplatin than C34 cells that do not express CYP2E1. In this study, we found that this sensitivity was due to an earlier activation of ERK in the E47 cells than in C34 cells. Glutathione depletion by L-buthionine sulfoximine (BSO) enhanced cisplatin cytotoxicity via increasing production of reactive oxygen species (ROS) and activation of ERK. In contrast, elevation of glutathione by glutathione ethyl ester (GSHE) decreased cisplatin/BSO cytotoxicity by decreasing ROS production and ERK activation. Inhibition of ERK activation by U0126 protected against cisplatin/BSO cytotoxicity via inhibiting ROS production but not restoring intracellular glutathione content. Examination of the mode of cell death showed that U0126 inhibited cisplatin-induced necrosis but not apoptosis. Cisplatin induced apoptosis was caspases-dependent; BSO switched cisplatin-induced apoptosis to necrosis via decreasing activities of caspases, and GSHE switched cisplatin/BSO induced necrosis back to apoptosis through maintaining activities of caspases. Similar to GSHE, U0126 partially switched cisplatin/BSO induced necrosis to apoptosis via restoring activities of caspases. Cisplatin lowered levels of thioredoxin, especially in the presence of BSO. Although U0126 failed in restoring intracellular glutathione levels, it restored thioredoxin levels which maintain activities of the caspases. These results suggest that thioredoxin can replace glutathione to promote the active thiol redox state necessary for caspase activity, and thus glutathione and thioredoxin regulate the mode of cisplatin toxicity in E47 cells via redox regulation of caspase activities.

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“…CDDP may also induce apoptosis by activating ASK1 (35). However, the potential clinical usefulness of CDDP is often limited by the acquisition of resistance to its cytotoxic actions, which may be due to its decreased uptake by the cancer cells, increased efflux from the cells, increased cellular DNA repair mechanisms, and increased levels of TRX, glutathione, or metallothionine (30,60,61). In the present study, a relatively high concentration of CDDP (50 M) induced the activation of apoptosis in Sham cells.…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin Is Downstream of Smad7 in a Pathway That Promotes Growth and Suppresses Cisplatin-Induced Apoptosis in Pancreatic Cancer

et al. 2004

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive human malignancy in which Smad7 is commonly overexpressed. Analysis by differential display identified thioredoxin-1 (TRX) as a gene whose basal expression is increased in COLO-357 pancreatic cancer cells engineered to overexpress Smad7. To delineate the biological consequences of TRX overexpression, we assessed TRX mRNA levels in PDAC and studied the effects of increased TRX levels in Smad7-overexpressing cells. By northern blotting, TRX mRNA levels were increased in PDAC samples by comparison with the normal pancreas. Moreover, analysis of lasercaptured pancreatic cancer cells revealed parallel increases in Smad7 and TRX mRNA levels. Retroviral infection of an antisense TRX cDNA suppressed TRX protein levels and blunted the increased capacity of Smad7-overexpressing cells to form colonies in soft agar. 1-Methyl-propyl-2-imidazolozyl disulfide, a TRX inhibitor, markedly suppressed the growth of sham-transfected COLO-357 cells and enhanced the growth inhibitory actions of cis-diamminedichloroplatinum(II) (CDDP). CDDP also induced apoptosis, as evidenced by induction of DNA laddering, PARP cleavage, and caspase-3/9 activities. These pro-apoptotic actions were greatly attenuated in Smad7-overexpressing cells, which exhibited a more prolonged association of TRX with the apoptosis inducer apoptosis signal-regulating kinase-1, and enhanced nuclear factor B activation in response to CDDP. These findings suggest that TRX is downstream of Smad7 in a pathway that confers a growth advantage to pancreatic cancer cells and that increases their resistance to CDDP-mediated apoptosis, implying novel regulatory functions for Smad7.

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Analysis of the inhibition of mammalian thioredoxin, thioredoxin reductase, and glutaredoxin by cis -diamminedichloroplatinum (II) and its major metabolite, the glutathione-platinum complex

Cited by 157 publications

References 52 publications

Sensitizing Effect of Galectin-7 in Urothelial Cancer to Cisplatin through the Accumulation of Intracellular Reactive Oxygen Species

Sensitizing Effect of Galectin-7 in Urothelial Cancer to Cisplatin through the Accumulation of Intracellular Reactive Oxygen Species

The mode of cisplatin-induced cell death in CYP2E1-overexpressing HepG2 cells: Modulation by ERK, ROS, glutathione, and thioredoxin

Thioredoxin Is Downstream of Smad7 in a Pathway That Promotes Growth and Suppresses Cisplatin-Induced Apoptosis in Pancreatic Cancer

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