Abstract
Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited the proliferation of LNCaP, PC-3, 22RV1 and DU-145 prostate cancer cells in a dose dependent manner. Furthermore, Annexin-V staining demonstrated that piperine treatment induced apoptosis in hormone dependent prostate cancer cells (LNCaP). Using global caspase activation assay, we show that piperine-induced apoptosis resulted in caspase activation in LNCaP and PC-3 cells. Further studies revealed that piperine treatment resulted in the activation of caspase-3 and cleavage of PARP-1 proteins in LNCaP, PC-3 and DU-145 prostate cancer cells. Piperine treatment also disrupted androgen receptor (AR) expression in LNCaP prostate cancer cells. Our evaluations further show that there is a significant reduction of Prostate Specific Antigen (PSA) levels following piperine treatment in LNCaP cells. NF-kB and STAT-3 transcription factors have previously been shown to play a role in angiogenesis and invasion of prostate cancer cells. Interestingly, treatment of LNCaP, PC-3 and DU-145 prostate cancer cells with piperine resulted in reduced expression of phosphorylated STAT-3 and Nuclear factor-κB (NF-kB) transcription factors. These results correlated with the results of Boyden chamber assay, wherein piperine treatment reduced the cell migration of LNCaP and PC-3 cells. Finally, we show that piperine treatment significantly reduced the androgen dependent and androgen independent tumor growth in nude mice model xenotransplanted with prostate cancer cells. Taken together, these results support further investigation of piperine as a potential therapeutic agent in the treatment of prostate cancer.
Highlights
Western men are confronted with an increasing incidence of cancer and cancer related deaths annually
Our results showed that DU-145 and PC-3 PCa (Figure 5B) cells treated with 160 mM and 75 mM of piperine dose respectively resulted in the downregulation of Nuclear factor-kB (NF-kB) and phosphorylated STAT-3 expression levels, underscoring the anti-cancer effects of piperine in prostate cancer cells
In the present study, we sought to evaluate the efficacy of piperine as anti-cancer agent against both androgen dependent and independent prostate cancer cell lines and investigate the molecular mechanisms responsible for its anti-proliferative activities
Summary
Western men are confronted with an increasing incidence of cancer and cancer related deaths annually. Statistics indicate that prostate cancer is the second leading cause of cancer related deaths among the men in United States. According to the recent estimates in the United States, 217,730 men will be newly diagnosed with prostate cancer and 32,050 men will die of this disease in 2010 [1]. Prostate cancer initially begins as being hormone dependent but as the disease progresses it transitions into being hormone independent and resistant to hormone related treatment. There is a great deal of interest in identifying natural compounds in the treatment of prostate cancer. In the United States alone, the average daily intake of black pepper has been estimated at 359 mg. Piperine accounts for 5% to 9% of the black pepper content, implying the daily intake of approximately 60–110 mM [4].
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