Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells

European Journal of Pharmacology
Li-heng HuangJikai Jiang

Abstract

Gossypol is an attractive therapeutic anti-tumor agent as an apoptosis inducer and is being evaluated in preclinical tests. However, the molecular mechanisms underlying apoptosis induction by gossypol in malignant cells have not been completely enunciated. Here we investigate the alterations of Bcl-2/Bcl-xL/Mcl-1 protein levels and Bcl-2 phosphorylation in gossypol-induced apoptosis in human leukemia HL-60 cells. We found that gossypol treatment inhibited cell growth and induced apoptosis in HL-60 cells. Bcl-2/Bcl-xL/Mcl-1 protein levels were slightly reduced and phosphorylation of Bcl-2 at threonine 56 (phospho T56) was not altered. However, phosphorylation of Bcl-2 at serine 70 (phospho S70) was strikingly down-regulated in gossypol-exposed cells. This reduction was found to be not only in both dose- and time-dependent fashion but also obviated by phorbol l2,13-dibutyrate (PDBu), an activator of protein kinase C (PKC). In addition, pre-treatment of PDBu partially prevented gossypol-induced apoptosis in HL-60 cells. Collectively, gossypol treatment can reduce phosphorylation of Bcl-2 at serine 70 in leukemia HL-60 cells and gossypol may be a promising therapeutical candidate for leukemia patients especially expressing phosphor...Continue Reading

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Citations

Feb 26, 2013·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Zhicheng LiuNaisheng Zhang
Jun 24, 2014·Mitochondrion·Stephen Jun Fei ChongShazib Pervaiz
Jan 13, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Dong-Oh MoonGi-Young Kim
Apr 8, 2014·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jill A P Spijkers-HagelsteinRonald W Stam
Jan 29, 2013·International Immunopharmacology·Meixia HuoGefu Chi
Dec 23, 2014·PloS One·Landa Zeenelabdin Ali SalimSyam Mohan
Nov 9, 2016·International Journal of Radiation Biology·Keishiro TomodaGlen S Kwon
Aug 23, 2018·Journal of Cellular Biochemistry·Bai YuquanZhao Jinping
Apr 10, 2016·Biological Chemistry·Yi Hui YeeShazib Pervaiz

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