title: Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells.
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 phosphorylated Bcl-2 at Ser70.
authors.affiliation: Department of Biochemistry, School of Medicine, Shantou University, China.
authors.forename: Li-heng
authors.initials: LH
authors.lastname: Huang
authors.forename: Jia-qi
authors.initials: JQ
authors.lastname: Hu
authors.forename: Wei-qun
authors.initials: WQ
authors.lastname: Tao
authors.forename: Yuan-hong
authors.initials: YH
authors.lastname: Li
authors.forename: Guan-ming
authors.initials: GM
authors.lastname: Li
authors.forename: Pei-yi
authors.initials: PY
authors.lastname: Xie
authors.forename: Xiao-shan
authors.initials: XS
authors.lastname: Liu
authors.forename: Jikai
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D020536:Enzyme Activators / Q000494:pharmacology; D019254:Genes, bcl-2; D006072:Gossypol / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D020536:Enzyme Activators; D019253:Proto-Oncogene Proteins c-bcl-2; D015240:Phorbol 12,13-Dibutyrate; D011065:Poly(ADP-ribose) Polymerases; D011493:Protein Kinase C; D006072:Gossypol