Gossypol induces spermidine/spermine N1-acetyltransferase in canine prostate epithelial cells

Gossypol is an antisteroidogenic compound naturally found in cottonseed. Gossypol has been shown to inhibit steroidogenesis in the canine prostate and may inhibit canine prostate growth. Its mechanism of action, however, is largely unknown. Our laboratory has previously demonstrated that in vivo administration of gossypol to male dogs can reduce circulating levels of testosterone and estradiol. Gossypol also showed an ability to reduce prostate weights. To search for genes regulated by gossypol in the canine prostate, differential display RT-PCR was performed on total RNAs isolated from control and gossypol-treated male dogs. Gossypol was demonstrated to induce expression of spermidine/spermine-N1-acetyl-transferase (SSAT), the major catabolic enzyme for polyamines. This induction was confirmed by Northern hybridization analysis of total RNA isolated from prostates of mature dogs treated with gossypol for 2 months. Gossypol was also shown to inhibit the progression of cells into the S phase mediated by spermidine. Our findings support the notion that gossypol can inhibit prostate cell proliferation and may be a potential therapeutic agent for use in controlling overgrowth of the prostate.