title: Gossypol-Induced Differentiation in Human Leukemia HL-60 Cells.
abstract: The main treatment of leukemia is traditional radiochemotherapy, which is associated with serious side effects. In the past twenty years, differentiation was found as an important effective measure to treat leukemia with fewer side effects. Gossypol, a natural compound which has been used as an effective contraceptive drug, has been proposed to be a potent drug to treat leukemia, but the differentiation effect has not been studied. In the present study, we investigated the pro-differentiated effects, in vitro, of gossypol on the classic human myeloid leukemia HL-60 cell line. The effects of gossypol were investigated by using morphological changes, nitroblue tetrazolium (NBT) reduction, surface markers, cell-cycle analysis and Western blot analysis, etc. When HL-60 cells were incubated with low concentrations of gossypol (2-5μM) for 48hr, a prominent G0/G1 arrest was observed. At 96 hr of treatment, 90% of HL-60 cells differentiated, as evidenced by morphological changes, NBT reduction, and increase in cell surface expression of some molecules were detected. This study is the first to identify gossypol's pro-differentiated effects on the leukemia cell line, and it induced differentiation through the PBK (PDZ-binding kinase)/TOPK (T-LAKcell-originated protein kinase) (PBK/TOPK) pathway. It is concluded that gossypol could induce differentiation in the leukemia HL-60 cells, and it may be a potential therapeutic agent, chemoprevention or chemotherapeutic adjuvant especially in combination drug therapy for leukemia.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi Provience, P. R. China; ; Department of Hematology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi Provience, P. R. China.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Qing-Xian
authors.initials: QX
authors.lastname: Bai
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Liu
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhang
authors.forename: Juan-Hong
authors.initials: JH
authors.lastname: Wang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuan-Fei
authors.initials: YF
authors.lastname: Li
authors.forename: Xie-Qun
authors.initials: XQ
authors.lastname: Chen
authors.forename: Gao-Sheng
authors.initials: GS
authors.lastname: Huang
keywords: differentiation; drug effects; gossypol; leukemia