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Abstract Title:

ABT-737 sensitizes curcumin-induced anti-melanoma cell activity through facilitating mPTP death pathway.

Abstract Source:

Biochem Biophys Res Commun. 2015 Jun 24. Epub 2015 Jun 24. PMID: 26116776

Abstract Author(s):

Teng Yu, Chao Chen, Yang Sun, Hui Sun, Tian-Hang Li, Jin Meng, Xianhua Shi

Article Affiliation:

Teng Yu

Abstract:

In the current study, we studied the potential role of ABT-737, a novel Bcl-2 inhibitor, on curcumin-induced anti-melanoma cell activity in vitro. The associated mechanisms were also investigated. We demonstrated that ABT-737 significantly sensitized curcumin-induced activity against melanoma cells (WM-115 and B16 lines), resulting in substantial cell death and apoptosis with co-administration. At the molecular level, curcumin and ABT-737 synergistically induced mitochondrial permeability transition pore (mPTP) opening in melanoma cells, the latter was evidenced by mitochondrial membrane potential (MPP) reduction and mitochondrial complexation between cyclophilin-D (CyPD) and adenine nucleotide translocator 1 (ANT-1). Significantly, mPTP blockers, including cyclosporin A and sanglifehrin A, remarkably inhibited curcumin and ABT-737 co-administration-induced cytotoxicity against melanoma cells. Meanwhile, siRNA-mediated knockdown of CyPD or ANT-1, the two key components of mPTP, alleviated WM-116 cell death by the co-treatment. Collectively, we show that ABT-737 sensitizes curcumin-induced anti-melanoma cell activity probably through facilitating mPTP death pathway. ABT-737 could be further investigated as a potential curcumin adjuvant in melanoma and other cancer treatment.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Apoptotic : CK(5217) : AC(3846)

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Sayer Ji
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