alexa Methyl jasmonate sensitizes human bladder cancer cells to gambogic acid-induced apoptosis through down-regulation of EZH2 expression by miR-101.
Genetics & Molecular Biology

Genetics & Molecular Biology

Gene Technology

Author(s): Wang Y, Xiang W, Wang M, Huang T, Xiao X,

Abstract Share this page

Abstract BACKGROUND AND PURPOSE: Gambogic acid (GA) and methyl jasmonate (MJ) are increasingly being recognized as novel natural anticancer compounds. Here, we investigated the antitumour effects of GA in combination with MJ on human bladder cancer cells. EXPERIMENTAL APPROACH: Cell viability was detected by cell counting kit-8 assay. Cell apoptosis was assessed by Hoechst 33258 staining and flow cytometry. Protein levels were determined by immunoblotting and expressions of mRNA and miRNAs by RT-PCR. Differential expressions of a group of downstream genes were identified using microarray analysis. KEY RESULTS: MJ significantly sensitized bladder cancer cells to GA-induced growth inhibition and apoptosis while sparing normal fibroblasts. MJ enhanced GA-induced activation of caspase-3 and caspase-9, and down-regulated the expression of XIAP. Furthermore, treatment of bladder cancer cells with a combination of GA and MJ induced synergistic inhibition of the enhancer of zeste homologue 2 (EZH2) expression, whereas miR-101 expression was up-regulated. Conversely, knockdown of miR-101 restored this decreased expression of EZH2 and suppressed the inhibitory effect of GA and MJ on the growth of bladder cancer cells. Microarray analysis showed that genes closely associated with bladder cancer development were significantly down-regulated by GA and MJ. In a s.c. xenograft mouse model of human bladder carcinoma, the combination of GA and MJ exerted an increased antitumour effect compared with GA alone. CONCLUSION AND IMPLICATIONS: MJ sensitizes bladder cancer cells to GA-induced apoptosis by down-regulating the expression of EZH2 induced by miR-101. Thus, the combination of selective anti-cancer agents MJ and GA could provide a novel strategy for treating human bladder cancer. © 2013 The British Pharmacological Society.
This article was published in Br J Pharmacol and referenced in Gene Technology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 3rd World Congress on Human Genetics
    August 14-15, 2017 Edinburgh, Scotland
  • 2nd International Conference and Expo on Generic Drug Market and Contract Manufacturing
    September 25-26, 2017 Frankfurt, Germany
  • 6th International Conference and Exhibition on Cell and Gene Therapy
    Mar 27-28, 2017 Madrid, Spain
  • 2nd World Congress on Human Genetics & Genetic Disorders
    November 02-03, 2017 Toronto, Canada

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version