β-Phenylethyl isothiocyanate reverses platinum resistance by a GSH-dependent mechanism in cancer cells with epithelial-mesenchymal transition phenotype

Wu, Wen; Zhang, Yan; Zeng, Zhao Lei; Li, Xiao Bing; Hu, Kai; Luo, Hui; Yang, Jing; Huang, Peng; Xu, Rui‐Hua

doi:10.1016/j.bcp.2012.11.017

Cited by 49 publications

(39 citation statements)

References 42 publications

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“…Previous studies have demonstrated that binding of GSH to cisplatin causes the formation of a Pt(GS)2 conjugate which is exported to outside of cancer cells by multidrug resistance-associated proteins (MRPs), thus reducing the level of cellular platinum [9,10]. Consistently, other studies showed that increased GSH level is a major factor associated with cisplatin resistance [11][12][13]. Cysteine is a rate-limiting precursor for GSH synthesis.…”

Section: Introductionmentioning

confidence: 92%

“…Cysteine is chemically unstable, and cells normally use the stable cystine as a precursor for GSH synthesis. The xc − system, composed of xCT (the light chain and the active subunit) and F42hc (the heavy chain subunit), is essential in maintaining intracellular cysteine/cystine levels by mediating uptake of cystine [13][14][15]. Therefore, inhibition of xc − would suppress GSH synthesis and consequently overcome GSH mediated resistance to cisplatin.…”

Section: Introductionmentioning

confidence: 98%

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Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism

et al. 2015

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 98%

Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism

et al. 2015

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“…Cancer cells may become resistant to platinum-based drugs through multiple mechanisms, including an increased ability to repair platinum-induced DNA damage, neutralization of platinum toxicity, and an increase in drug export (38). GSH, the most abundant cellular antioxidant, is important in the promotion of cell survival.…”

Section: Discussionmentioning

confidence: 99%

The effects of buthionine sulfoximine on the proliferation and apoptosis of biliary tract cancer cells induced by cisplatin and gemcitabine

Yin

Wang

et al. 2015

Oncology Letters

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Abstract.Patients with biliary tract cancer (BTC) have a poor prognosis. Advanced BTC patients have been treated with cisplatin in combination with gemcitabine, however, the treatment has had little impact on survival rates, and more effective treatments are urgently required for this disease. Previous studies discovered that buthionine sulfoximine (BSO), a potent inhibitor of glutathione (GSH) synthesis, was able to enhance the cytotoxic effect of various drugs in cancer cells. Phase I studies demonstrated that continuous-infusion of BSO was relatively non-toxic and resulted in the depletion of tumor GSH. However, the synergistic effect of BSO and cisplatin in BTC cells remains unknown, and no reports are available regarding sensitization to gemcitabine by BSO. In the present study, the effect of BSO in combination with cisplatin or gemcitabine in the treatment of BTC cells was examined in vitro. Cytotoxic effects were measured using an MTT assay, Annexin V assay and fluorescence-activated cell sorting analysis. Antiapoptotic protein expression levels were examined using western blot analysis. The results revealed that a sub-toxic concentration of BSO was capable of significantly enhancing cisplatin-induced apoptosis in BTC cells. The mechanisms of BSO's effect on BTC cells may be attributable to the reduction of GSH levels and downregulation of the expression of antiapoptotic proteins (Bcl-2, Bcl-xL and Mcl-1). Furthermore, BSO enhanced the antiproliferative effect of gemcitabine. In conclusion, the present data are the first results to indicate that BSO may sensitize BTC cells to standard first-line chemotherapeutic agents (cisplatin and gemcitabine). Combining BSO with cisplatin and gemcitabine is a promising therapeutic strategy for the treatment of BTC.

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“…ITCs show synergistic activity when combined with common chemotherapeutic agents like cisplatin, paclitaxel, metformin, Adriamycin, etoposide, vorinostat, and docetaxel [140,[142][143][144]. Combination of BITC or PEITC with cisplatin did not affect DNA platination but enhanced the apoptotic effects by depletion of β-tubulin [141,143].…”

Section: Combination Therapymentioning

confidence: 95%

“…Due to its wide range of cellular targets, ITCs can be utilized for combinatorial therapeutic approaches. Combination of ITCs with conventional chemotherapeutic agents has been tested in preclinical models [19,[139][140][141].…”

Section: Combination Therapymentioning

confidence: 99%

Mechanisms of the Anticancer Effects of Isothiocyanates

et al. 2015

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β-Phenylethyl isothiocyanate reverses platinum resistance by a GSH-dependent mechanism in cancer cells with epithelial-mesenchymal transition phenotype

Cited by 49 publications

References 42 publications

Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism

Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism

The effects of buthionine sulfoximine on the proliferation and apoptosis of biliary tract cancer cells induced by cisplatin and gemcitabine

Mechanisms of the Anticancer Effects of Isothiocyanates

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