Quercetin-6-C-β-D-glucopyranoside, natural analog of quercetin exhibits anti-prostate cancer activity by inhibiting Akt-mTOR pathway via aryl hydrocarbon receptor

被引：33

作者：

Hamidullah ^{[1
]}

Kumar, Rajeev ^{[1
]}

Saini, Karan Singh ^{[1
]}

Kumar, Amit ^{[1
]}

Kumar, Sudhir ^{[2
]}

Ramakrishna, E. ^{[2
]}

Maurya, Rakesh ^{[2
,3
]}

Konwar, Rituraj ^{[1
,3
]}

Chattopadhyay, Naibedya ^{[1
,3
]}

机构：

[1] CSIR Cent Drug Res Inst CDRI, Div Endocrinol, Lucknow 226031, Uttar Pradesh, India

[2] CSIR Cent Drug Res Inst, Med & Proc Chem Div, Lucknow 226031, Uttar Pradesh, India

[3] AcSIR, New Delhi 110001, India

来源：

BIOCHIMIE | 2015年 / 119卷

关键词：

Prostate cancer; Quercetin-6-C-beta-D-glucopyranoside (QCG); Cell cycle; Apoptosis; Aryl hydrocarbon receptor; Akt/mTOR; CYCLIN-DEPENDENT KINASES; CELL-CYCLE; IN-VIVO; APOPTOSIS; FLAVONOIDS; ACTIVATION; EXPRESSION; TOXICITY; GROWTH; RESVERATROL;

D O I：

10.1016/j.biochi.2015.10.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pre-clinical studies suggest mitigating effect of dietary flavonoid quercetin against cancer and other diseases. However, quercetin suffers from poor metabolic stability, which appears to offset its pharmacological efficacy. Recently, we isolated quercetin-6-C-beta-D-glucopyranoside (QCG) from Ulmus wallichiana planchon that has greater stability profile over quercetin. In the present study, the cytotoxic and apoptotic effects of QCG on prostate cancer cells were assessed. QCG inhibited prostate cancer cell proliferation by arresting cells at G0/G1 phase of cell cycle and induces apoptosis as evident from cytochrome c release, cleavage of caspase 3 and poly (ADP-ribose) polymerase. Mechanistic studies revealed that QCG inhibited reactive oxygen species (ROS) generation and Akt/mTOR cell survival pathways. Aryl hydrocarbon receptor (AhR) was a critical mediator of QCG action as knockdown of AhR attenuated QCG-induced cell cycle arrest, apoptosis and inhibition of Akt/mTOR pathway in prostate cancer cells. Taken together, our results suggest that QCG exhibits anti-cancer activity against prostate cancer cells via AhR-mediated down regulation of Akt/mTOR pathway in PC-3 cells. (C) 2015 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

引用

页码：68 / 79

页数：12

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