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Capsaicin Inhibits the Growth of Prostate Cancer Cells

Figure 4. Capsaicin inhibits NF-nB promoter activity of PC-3 cells. A, PC-3 cells were transfected with NF-nB-Luc reporter gene. Following transfections, cells were incubated either with or without capsaicin (2 104 mol/L) for either 24 or 48 hours. Columns, means of three or more experiments; bars, FSD. B, Western blot analysis of NF-nB expression in PC-3 cells. Cells were incubated with capsaicin (2 104 mol/L) for either 2 or 4 hours. Whole cell extract or nuclear proteins were assayed for expression of the p65 subunit of NF-nB and either GAPDH or hnRNP A1 (nuclear protein–specific control), respectively. C, PC-3 cells were examined for their subcellular localization of p65 after incubation either with (right) or without (left) capsaicin (2 104 mol/L, 4 hours). D, effect of capsaicin on TNF-induced degradation of InBa in PC-3 cells. PC-3 cells, either untreated or pretreated with capsaicin (2 104 mol/L, 3 hours), were further incubated for either 15 or 30 minutes with TNF (20 ng/mL), and assayed by Western blot for InBa in the cytoplasmic fraction. E, effect of capsaicin on InBa in the cytoplasm. Cells were incubated with capsaicin (1 or 2 104 mol/L, 2 hours). Cytoplasmic proteins were harvested and assayed for expression of the InBa and GAPDH.

only of wild-type p53 expressing LNCaP cells, but also p53-null PC-3 cells and p53-mutant DU-145 cells (25). Therefore, capsaicin could have in vitro and in vivo antiproliferative activity indepen- dent of p53 activity. Nevertheless, in the wild-type p53 expressing LNCaP cells, capsaicin induced p53, and its targets Bax and p21 in a time-dependent manner.

In further studies, we showed that capsaicin inhibited the NF-nB pathway. Previous studies have shown that the NF-nB signaling pathway is constitutively active in the hormone-independent prostate cancer cell lines, PC-3 and DU-145, but not in the

hormone-responsive LNCaP cells (13). We confirmed that the NF-nB transcriptional activity is constitutively robust in PC-3 cells as shown by their stimulation of a reporter gene containing NF-nB binding sites. However, this activity of NF-nB was dramatically inhibited by capsaicin. We also showed that capsaicin inhibited the TNF-a-induced InBa degradation in the cytoplasm, thus prevent- ing the TNF-a-dependent translocation of NF-nB to the nucleus. Furthermore, InBa protein levels increased in PC-3 cells cultured with capsaicin for 2 hours compared with the levels in untreated cells. Taken together, these results suggest that capsaicin either



Cancer Res 2006; 66: (6). March 15, 2006

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