Inhibition of human prostate cancer cells growth by gossypol is associated with stimulation of transforming growth factor-beta.
Gossypol (GP), an antifertility agent in males, is also capable of inhibiting the proliferation of a wide range of cancer cells in vivo and in vitro. Thus, in this study we investigated the effect of GP on the growth of human androgen-independent prostate cancer cell line (PC3). The results showed that GP acts as a potent inhibitor of PC3 cells as determined by thymidine incorporation assay and flow cytometric analysis. Flow cytometry revealed that treatment of PC3 cells with GP resulted in a dose- and time-dependent accumulation of cells in the GO/GI phase with a concomitant decrease in cells progressing to the S and G2/M phase. These data support our thymidine incorporation results which indicated that GP is a potent inhibitor of PC3 cells. By ribonuclease protection assay, we also investigated the effect of GP on transforming growth factor-beta 1 (TGF-beta 1) gene expression in PC3 cells. Interestingly, the stimulatory effect of GP on TGF-beta 1 gene expression correlates well with its inhibitory effect on PC3 cell DNA synthesis and its ability to arrest cells in GO/G1 phase. Based on these data, it can be concluded that GP is a potent inhibitor of prostate cancer cell growth that acts by arresting cells in GO/G1 phase and that this inhibitory effect may be mediated by TGF-beta 1.
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, Ohio State University, Columbus 43210-1092, USA.
F
F
Shidaifat
H
H
Canatan
S K
SK
Kulp
Y
Y
Sugimoto
W Y
WY
Chang
Y
Y
Zhang
R W
RW
Brueggemeier
W J
WJ
Somers
Y C
YC
Lin
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D006072:Gossypol