Andrographolide induces degradation of mutant p53 via activation of Hsp70

International Journal of Oncology
Hirofumi SatoHirokazu Noshiro

Abstract

The tumor suppressor gene p53 encodes a transcription factor that regulates various cellular functions, including DNA repair, apoptosis and cell cycle progression. Approximately half of all human cancers carry mutations in p53 that lead to loss of tumor suppressor function or gain of functions that promote the cancer phenotype. Thus, targeting mutant p53 as an anticancer therapy has attracted considerable attention. In the current study, a small-molecule screen identified andrographlide (ANDRO) as a mutant p53 suppressor. The effects of ANDRO, a small molecule isolated from the Chinese herb Andrographis paniculata, on tumor cells carrying wild-type or mutant p53 were examined. ANDRO suppressed expression of mutant p53, induced expression of the cyclin-dependent kinase inhibitor p21 and pro-apoptotic proteins genes, and inhibited the growth of cancer cells harboring mutant p53. ANDRO also induced expression of the heat-shock protein (Hsp70) and increased binding between Hsp70 and mutant p53 protein, thus promoting proteasomal degradation of p53. These results provide novel insights into the mechanisms regulating the function of mutant p53 and suggest that activation of Hsp70 may be a new strategy for the treatment of cancers har...Continue Reading

References

Jul 2, 1992·Nature·D P Lane
Nov 5, 1999·Advances in Cancer Research·P Hainaut, M Hollstein
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Feb 6, 2004·The Journal of Biological Chemistry·Zhuo ZhangRuiwen Zhang
Jul 7, 2005·The Journal of Biological Chemistry·Vladimir J N BykovKlas G Wiman
Aug 17, 2005·Cancer Research·Mikhail V BlagosklonnyTito Fojo
Apr 16, 2008·Annual Review of Biochemistry·Andreas C Joerger, Alan R Fersht
May 17, 2008·Genes & Development·Tamara TerzianGuillermina Lozano
Dec 27, 2008·International Immunopharmacology·Ala'a A Abu-GhefrehCharles I Ezeamuzie
May 5, 2009·Cancer Cell·Jeremy M R LambertVladimir J N Bykov
Jan 27, 2011·Journal of Cellular Biochemistry·Jia WangQing-long Guo
May 26, 2012·Cancer Cell·Xin YuDarren R Carpizo
Jan 31, 2013·Nature Communications·Christopher D WassmanRommie E Amaro
Jan 10, 2014·Drug Delivery·Amol D ThingaleChellampillai Bothiraja
Apr 11, 2014·International Journal of Biological Sciences·Qian-Qian ZhangLi-Jing Wang
Sep 11, 2014·Journal of Cancer Research and Therapeutics·Qingmin Xia, Weimin Mao
Sep 19, 2015·Scientific Reports·Phitchayapak WintachaiDuncan R Smith
Dec 29, 2015·Molecular Medicine Reports·Hui Gao, Jianrong Wang

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