Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get two FREE E-Books

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

Amurensin G, a novel SIRT1 inhibitor, sensitizes TRAIL-resistant human leukemic K562 cells to TRAIL-induced apoptosis.

Abstract Source:

Biochem Pharmacol. 2012 Aug 1 ;84(3):402-10. Epub 2012 Mar 29. PMID: 22483777

Abstract Author(s):

Hak-Bong Kim, Mi-Ju Kim, Su-Hoon Lee, Jae-Won Lee, Jae-Ho Bae, Dong-Wan Kim, Trong Tuan Dao, Won Keun Oh, Chi-Dug Kang, Sun-Hee Kim

Article Affiliation:

Hak-Bong Kim

Abstract:

Many types of cancer cells remain resistant towards TRAIL-induced cytotoxicity by the blockade of apoptotic signaling cascades. Thus, sensitizers are needed to enhance the effect of TRAIL-based cancer therapies. Although synergistic tumor cell death has been reported when various HDAC inhibitors were administered with TRAIL in a variety of human cancers, the effect of inhibitors of Class III HDAC such as SIRT1 have not been reported. We reported here for the first time that inhibition of SIRT1 augmented the cytotoxic and apoptotic effects of TRAIL on human leukemic K562 cells. Knockdown of SIRT1 or treatment with amurensin G, a potent new SIRT1 inhibitor, up-regulated the levels of DR5 and c-Myc and down-regulated the level of c-FLIP(L/S). Furthermore, knockdown of SIRT1 or treatment with amurensin G augmented the molecular responses to TRAIL, including activation of caspase-8, -9 and -3, PARP cleavage, up-regulation of Bax, and down-regulation of Bcl-2. Amurensin G-enhanced TRAIL-induced apoptosis was abrogated by caspase inhibitor Z-VAD-FMK. These findings suggest that the suppression of SIRT1 with siRNA or amurensin G sensitize the TRAIL-resistant K562 cell to TRAIL-induced apoptosis, possibly by the up-regulation of c-Myc and DR5 surface expression and the down-regulations of c-FLIP and Mcl-1. In addition, amurensin G, a potent new SIRT1 inhibitor, would be used as a sensitizer of TRAIL in TRAIL-resistant leukemic cells.

Print Options


Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get two FREE E-Books

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Depression: 21st Century Solutions + The Dark Side of Wheat

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2019 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.