Abstract
Prostate cancer (PCa) is the second leading cause of death in American men. The chemotherapeutic treatment strategies are generally not effective and can lead to side effects. Hence, there is an urgent need to identify novel chemotherapeutic agents. The aim of this study was to synthesize and evaluate the therapeutic effects of a synthetic analog of polygodial (PG), a pungent constituent abundantly present in mountain pepper, water pepper and dorrigo pepper, on LNCaP PCa cell line and its anti-cancer mechanisms in a preclinical study. We evaluated the anti-cancer potential of the PG analog namely DRP-27 using various assays such as cell viability by MTT assay, anchorage independent growth by soft agar assay, reactive oxygen species generation by 2',7'-dichlorofluorescein probe-based fluorescence assay, and apoptosis by Annexin-V and TUNEL assays respectively. Western blot analysis was performed to identify the molecular mechanism of DRP-27-induced cell death. Our results showed that DRP-27 significantly inhibited LNCaP cell proliferation in a dose-dependent manner at 48 h treatment in vitro. In addition, DRP-27 potently inhibited anchorage-independent growth of these cells. Flow cytometry, Annexin-V and TUNEL assays confirmed that DRP-27 induces apoptosis in LNCaP cells. DRP-27 also induced the activation of intracellular reactive oxygen species. Western blot analysis revealed that DRP-27 downregulated the expression of survivin, while activating Bax and DNA damage marker pH(2)AX in LNCaP cells. In conclusion, our study suggests that DRP-27 might be an effective anti-cancer agent for PCa.