We evaluated the chemotherapeutic efficacy of racemic gossypol (GP), an antifertility agent, on prostate cancer and the role of estrogen on canine BPH. GP was shown to inhibit growth and metastasis of prostate cancer cells in the in vitro system. Effect of GP on the growth of prostatic cancer cells may be mediated by inducing production of transforming growth factor-beta1 in prostate cancer cells. Transforming growth factor-beta1, in turn, can regulate the expression of cell cycle regulatory protein cyclin D1 that regulate cell cycle progression of prostate cancer cells. Gossypol (-) [GP (-)] and cottonseed oil, like GP, also exhibit similar anti-proliferative effects on the prostatic cancer cells. Moreover, the inhibitory dose of GP (-) and cottonseed oil have a greater potency than that of GP. GP was also shown to inhibit the O2 consumption and CO2 production in prostate cancer cells. This inhibition may relate to inhibiting mitochondrial succinic dehydrogenase activity in those cells.
Recently, we isolated a novel subline of the MAT-LyLu cells isolated from metastasized lungs of MAT-LyLu bearing Copenhagen rats (MLL cell). MLL cells displayed more invasive properties than MAT-LyLu cell, while MLL cells possessed lower mRNA levels of nm23, a metastasis suppressor gene, than MAT-LyLu cells. Both MLL and MAT-LyLu cells were susceptible to GP, which induced a dose-dependent inhibition of invasive activity with increasing the expression of nm23 mRNA. The invasive inhibition of GP on MLL and MAT-LyLu cells might be mediated by elevating the expression of nm23 metastasis suppressor gene.
Experimentally, estrogens are associated with human BPH. The increase in the proliferation of canine prostatic stromal cells and the decrease in the estrogen receptor beta mRNA expression of canine prostatic cells with ages were observed. The age-dependent and cell-specific difference in the mRNA expression of estrogen receptor beta in canine prostate may contribute to the proliferative imbalance between epithelial/stromal cells of aging dogs, associated with the development of canine BPH. Also, the response of canine prostatic cells to 17 beta-estradiol (E2) treatment is cell-specific and age-dependent.