Premium
Resveratrol Increases Anti‐Proliferative Activity of Bestatin Through Downregulating P‐Glycoprotein Expression Via Inhibiting PI3K/Akt/mTOR Pathway in K562/ADR Cells
Author(s) -
Wang Li,
Wang Changyuan,
Jia Yongming,
Liu Zhihao,
Shu Xiaohong,
Liu Kexin
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25407
Subject(s) - resveratrol , pi3k/akt/mtor pathway , protein kinase b , chemistry , k562 cells , intracellular , apoptosis , p glycoprotein , pharmacology , cell growth , cancer research , phosphorylation , signal transduction , microbiology and biotechnology , biology , multiple drug resistance , biochemistry , antibiotics
Multidrug resistance (MDR) is a major obstacle in the clinical therapy of hematological malignancies. P‐glycoprotein (P‐gp) overexpression results in reduction of intracellular drug concentration with a consequence that the cytotoxicity of anti‐tumor drugs is decreased, which leads to MDR in K562/ADR cells. In this study, we found that resveratrol enhanced the anti‐proliferative activity of bestatin in K562/ADR cells. Co‐treatment with resveratrol, IC 50 values of bestatin in K562/ADR cells significantly decreased and activation of caspase‐3 and caspase‐8 increased, which indicated that resveratrol potentiated bestatin‐induced apoptosis. Resveratrol increased the intracellular concentration of bestatin through inhibiting P‐gp function and downregulating P‐gp expression at mRNA and protein levels, which increased anti‐proliferative activity of bestatin in K562/ADR cells. Resveratrol decreased the phosphorylation of Akt and mTOR but did not affect the phosphorylations of JNK or ERK1/2. These results demonstrated that resveratrol could increase the anti‐proliferative activity of bestatin through downregulating P‐gp expression via suppressing the PI3K/Akt/mTOR signaling pathway. J. Cell. Biochem. 117: 1233–1239, 2016. © 2015 Wiley Periodicals, Inc.