Gossypol inhibits the growth of MAT-LyLu prostate cancer cells by modulation of TGFbeta/Akt signaling.
Gossypol (GP), a male contraceptive compound naturally present in cottonseed products, possesses anti-proliferative and anti-metastatic effects in vitro and in vivo. However, the detailed mechanisms responsible for the effects of GP on the cell cycle of prostate cancer cells remain to be elucidated. In the present study, we investigated the effects of GP on the regulation of the cell cycle of rodent prostate cancer MAT-LyLu cells and the mechanisms of GP-induced growth inhibition. Our results showed that GP inhibited the cell proliferation and colony formation in a dose-dependent manner by the up-regulation of expression and secretion of transforming growth factor beta1 (TGFbeta1) and down-regulation of expression of Akt and phospho-Akt protein. The inhibition of cell growth was also demonstrated by cell cycle arrest at G0/G1 phase. Furthermore, GP decreased the expression of cyclin D1, Cdk4 and phospho-Rb in MAT-LyLu cells. Thus, the inhibitory effects of GP on the proliferation of MAT-LyLu prostate cancer cells are associated with modulation of TGFbeta1 and Akt signaling, which influence the expression of regulatory proteins such as cyclin D1, Cdk4 and phospho-Rb which regulate cell cycle progression of prostate cancer cells.
Jiang
Jiahua
J
Cancer Research Laboratory, Methodist Research Institute, Clarian Health Partners Inc., Indianapolis, IN 46202, USA.
Ye
Weiping
W
Lin
Young C
YC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D019938:Cyclin D1 / Q000378:metabolism; D006072:Gossypol / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D003272:Contraceptive Agents, Male; D016160:Retinoblastoma Protein; D053773:Transforming Growth Factor beta1; D019938:Cyclin D1; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D006072:Gossypol