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J Jiang1 , SK Kulp1 *, Y Sugimoto1 , Y Zhang1 *, YC Lin1 *
Lab. Reprod. & Molec. Endocrinology, College of Vet. Med, The Ohio State Univ, Columbus, Ohio 1
Gossypol (GP), a polyphenolic compound naturally occurring in cottonseed, has gained interest as an anticancer agent. We have shown that GP inhibits in vitro growth of PC3, MCF-7 and primary cultured human prostate cells, as well as the in vivo tumor growth and lung and lymph node metastasis of the androgen-independent prostate cancer cell line, MAT-LyLu, after implantation into Copenhagen rats. Our previous results implicated the induction of TGF-1 mRNA expression as a mechanism of growth inhibition in PC3 human prostate cancer cells in vitro. The present study examined GP's effects on the growth of MAT-LyLu cells and its mechanism of action. For DNA synthesis, MAT-LyLu cells were treated with different concentrations of GP (0, 0.25, 0.5 and 1 ÁM) for 24 h, followed by 3 h treatment with 3H thymidine (5 Ci/ml). GP caused reductions in DNA synthesis of 33.4%, 53.2%, and 94.3% at 0.25, 0.5 and 1 M, respectively (p<0.05). Similarly, GP prolonged the doubling time of MAT-LyLu cells by 33%, 42% and 89.8% at 0.25, 0.5 and 1 M, respectively. RT-PCR revealed that GP at concentrations of 0.5 and 2.0 M induced 2-fold and 3-fold increases, respectively, in TGF-1 mRNA levels. ELISA results showed that, at a concentration of 4 M, GP caused a 3-fold increase in TGF-1 protein secretion. The results indicate that the inhibitory action of GP in MAT-LyLu cells involves the induction of TGF-1. Currently, we utilize the MAT-LyLu-Copenhagen rat system as an in vivo model of metastasis. We have isolated metastatic cells from the lungs of MAT-LyLu tumor-bearing Copenhagen rats which result in tumor growth upon reimplantation into this rodent prostate cancer model. This in vivo model will be used to continue our investigations of the effects of GP and other chemotherapeutic agents on metastasis. (NIH grants CA66193 and P30CA16058)
This abstract is being presented on Tuesday, August 3 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.