Molecular Effects of 13C/DIM in Prostate Cancer
Annual rept. 1 Apr 2004-31 Mar 2005
WAYNE STATE UNIV DETROIT MI
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We have previously shown anti-proliferative and pro-apoptotic effects of 13C and DIM through the NF- B pathway in prostate cancer cells. To further explore the molecular mechanisms involved in the regulation of NF- B by I3CDIM, we investigated the effects of B-DIM, a formulated DIM with greater bioavailability, on AR, Akt, and NF- B signaling in hormonesensitive LNCaP and hormone-insensitive C4-2B prostate cancer cells. We found that B-DIM significantly inhibited cell growth and induced apoptosis in both cell lines. By Akt transfection, RT-PCR, Western Blot analysis, and EMSA, we found that there could be a crosstalk between Akt, NF- B, and AR in cell signaling. Importantly, we found that B-DIM significantly inhibited Akt activation, NF- B DNA binding activity, and the expressions of AR and PSA, interrupting the crosstalk. Moreover, our confocal image study revealed that B-DIM inhibited AR nuclear translocation, leading to the down-regulation of AR target genes including PSA. These results suggest that B-DIM could inhibit cell growth and induce apoptosis partly through downregulation of AR, Akt and NF- B signaling. These results along with our previous findings suggest that 13C and DIM may be potent agents for the prevention andor treatment of androgen sensitive and androgen-refractory prostate cancers.
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