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Abstract Number: 3185
Anti-tumor activity of indole-3-carbinol in prostate cancer
Venkata P. S. Garikapaty, Ashok T. Badithe, Yuan-Gen Chen, Jing Lai, Abraham Mittelman, Raj Tiwari, New York Medical College, Valhalla, NY.
The phytoantiestrogen, indole-3-carbinol (I3C), present in cruciferous vegetables has anticancer activity in breast cancer using animal and in vitro cell culture models. In breast cancer, although the primary mechanism of action of I3C was directed towards estrogen responsive cells and estradiol mediated signal transduction processes, ubiquitous processes that involved kinases and down regulation of transcriptional factors were also shown to be molecular targets of I3C.
The anticancer effect of I3C when used as a therapeutic agent in prostate cancer is not known. We report the effect of I3C injected intra-peritoneally (i.p.) and intra-venously (i.v.) in Copenhagen rats using the transplantable androgen non-responsive metastatic cell line MAT-LyLu in Copenhagen rats. Indole-3-carbinol injected i.v. (0.1 mg/Kg body weight) and i.p. (0.4 mg/Kg) 2X weekly showed significant tumor reduction both in terms of tumor incidence and rate of tumor growth.
Tumors were initiated with 20,000 MAT-LyLu cells injected intra-dermally in Copenhagen rats. The latency of tumor induction was increased by more than seventy five percent. Fifty percent of the animals treated with I3C were tumor free and showed significant reduction in number of lung metastases.
Reduction in cyclin D1 levels and down regulation of the cell cycle related kinases cdk4 and cdk6 with a concomitant induction of apoptosis was observed in MAT-LyLu cells treated with I3C. These effects on rat prostate cancer cell were further extended to human prostate cancer cells.
Antiproliferative effect was noted on human prostate cancer cells, PC-3 and LnCaP with IC50 values comparable to MAT-LyLu.
Our studies clearly indicate a role for chemopreventive dietary agents as adjuvants in the treatment of prostate cancer, specifically for metastatic disease where continuous ingestion of I3C may reduce metastatic disease burden.
Further validation of our rat study in human prostate cancer xenograft model is underway.
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