Cancer therapyis mainly due to the marked increase in AR expression [44],[45],[46]. However, DU-145 and PC-3 cells do not express AR suggesting that AR independent survival mechanisms contributing in these cell types. Our results have shown that in LNCaP (AD) cells, piperine can down regulate both NF-kB and AR. Similarly, piperine reduced the expression of NF-kB in DU145 and PC-3 (AI) cells. These results indicate that piperine could HIF-2��-IN-1 site inhibit PCa of both AD and AI PCa cells. However, androgen dependent prostate cancer cells (LNCaP) were found to be more sensitive to piperine treatment due to downregulation of multiple targets such as AR, NF-kB and STAT-3 expression in these cells. Our results presented in this study also suggest that piperine could inhibit migration abilities of LNCaP and PC-3 prostate cancer cells which may be beneficial in preventing metastases. This notion is backed by the Boyden chamber assay, where inhibition of cell migration of LNCaP and PC-3 prostate cancer cells is observed following treatment with piperine. In support of our findings, previous studies have shown that piperine also has an inhibitory effect on invasion of B16-F10 melanoma cells via NF-kB inhibition [7]. The anti-proliferative effect of piperine was also confirmed in our in vivo studies, where tumor growth was substantially reduced 16985061 following piperine treatment in nude mice subcutaneously Title Loaded From File implanted with LNCaP and DU-145 cells. Based on our in vitro cell proliferation studies, we have selected the highly sensitive LNCaP and the least sensitive DU-145 cells for the comparison of efficacy of piperine treatment. Our results here show that piperine treatment (100 mg/kg body weight) via intraperitoneal injection against LNCaP xenotransplants resulted in a 72 reduction in tumor size as compared to the DU-145 treated group, where the reduction in tumor size was noted to be 41 . Interestingly, piperine at lower dose (10 mg/kg) administered via gavage treatment also inhibited LNCaP xenograft tumor growth by 38 . Hence, our in vivo results in nude mice correlated with our in vitro studies of piperine treated LNCaP and DU-145 cells. Previous studies have shown that piperine treatment 23148522 on PC-3 prostate cancer cells in vivo resulted in a non-statistically significant reduction in tumor size [4]. We, therefore, did not select PC-3 cells for our in vivo studies. Our in vitro data, however, suggests that piperine has an antiproliferative effect on PC-3 cells. Makhov et al treated mice only twice, once a week, with piperine [4] but did not observe any significant reduction in tumor growth. In our study, mice in the treatment group were treated daily with piperine for 4 weeks. The significant reduction in tumor growth that we observed may be due to the different treatment regimen (dose and daily injections) used in our in vivo studies. Moreover, the piperine concentration especially the gavage administration (10 mg/kg body weight) used in our study seems to be tolerable in humans based on the following dose extrapolation studies. We have made an attempt to derive the human equivalent dose (HED) based on our in vivo piperine concentration used in treating the mice. Recent studies advocate the use of body surface area (BSA) as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials [47]. Based on BSA, the daily HED of piperine (10 mg/kg) is 48.6 mg/day, a dose which is closer to previously studied tole.Cancer therapyis mainly due to the marked increase in AR expression [44],[45],[46]. However, DU-145 and PC-3 cells do not express AR suggesting that AR independent survival mechanisms contributing in these cell types. Our results have shown that in LNCaP (AD) cells, piperine can down regulate both NF-kB and AR. Similarly, piperine reduced the expression of NF-kB in DU145 and PC-3 (AI) cells. These results indicate that piperine could inhibit PCa of both AD and AI PCa cells. However, androgen dependent prostate cancer cells (LNCaP) were found to be more sensitive to piperine treatment due to downregulation of multiple targets such as AR, NF-kB and STAT-3 expression in these cells. Our results presented in this study also suggest that piperine could inhibit migration abilities of LNCaP and PC-3 prostate cancer cells which may be beneficial in preventing metastases. This notion is backed by the Boyden chamber assay, where inhibition of cell migration of LNCaP and PC-3 prostate cancer cells is observed following treatment with piperine. In support of our findings, previous studies have shown that piperine also has an inhibitory effect on invasion of B16-F10 melanoma cells via NF-kB inhibition [7]. The anti-proliferative effect of piperine was also confirmed in our in vivo studies, where tumor growth was substantially reduced 16985061 following piperine treatment in nude mice subcutaneously implanted with LNCaP and DU-145 cells. Based on our in vitro cell proliferation studies, we have selected the highly sensitive LNCaP and the least sensitive DU-145 cells for the comparison of efficacy of piperine treatment. Our results here show that piperine treatment (100 mg/kg body weight) via intraperitoneal injection against LNCaP xenotransplants resulted in a 72 reduction in tumor size as compared to the DU-145 treated group, where the reduction in tumor size was noted to be 41 . Interestingly, piperine at lower dose (10 mg/kg) administered via gavage treatment also inhibited LNCaP xenograft tumor growth by 38 . Hence, our in vivo results in nude mice correlated with our in vitro studies of piperine treated LNCaP and DU-145 cells. Previous studies have shown that piperine treatment 23148522 on PC-3 prostate cancer cells in vivo resulted in a non-statistically significant reduction in tumor size [4]. We, therefore, did not select PC-3 cells for our in vivo studies. Our in vitro data, however, suggests that piperine has an antiproliferative effect on PC-3 cells. Makhov et al treated mice only twice, once a week, with piperine [4] but did not observe any significant reduction in tumor growth. In our study, mice in the treatment group were treated daily with piperine for 4 weeks. The significant reduction in tumor growth that we observed may be due to the different treatment regimen (dose and daily injections) used in our in vivo studies. Moreover, the piperine concentration especially the gavage administration (10 mg/kg body weight) used in our study seems to be tolerable in humans based on the following dose extrapolation studies. We have made an attempt to derive the human equivalent dose (HED) based on our in vivo piperine concentration used in treating the mice. Recent studies advocate the use of body surface area (BSA) as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials [47]. Based on BSA, the daily HED of piperine (10 mg/kg) is 48.6 mg/day, a dose which is closer to previously studied tole.
