Computational Analysis and in vitro Validation of the Anti-Prostate Cancer Activity of Sesamin from Sesamum indicum.

INTRODUCTION: Prostate cancer is the fourth most commonly diagnosed cancer worldwide and the eighth leading cause of cancer-related mortality, primarily affecting elderly males. Conventional therapeutic approaches, while effective in some cases, often come with substantial side effects, posing particular challenges for older patients. As a result, the exploration of natural compounds from traditional Chinese medicine (TCM) as potential anticancer agents has gained increasing attention. Sesamin, a dietary lignan found in sesame seeds and frequently used in TCM, has shown promise in preliminary studies for its antioxidant, anti-inflammatory, and potential anticancer properties. However, its specific effects and underlying mechanisms against prostate cancer cells remain inadequately characterized.

MATERIALS AND METHODS: This study investigated the anticancer effects of sesamin on human prostate cancer DU145 cells. Cell viability was evaluated using MTT assays. Apoptosis induction and cell cycle distribution were assessed by flow cytometry. Protein expression levels of PPAR-γ, p21, and p53 were measured using Western blotting. Additionally, in silico molecular docking was performed using the LibDock algorithm to evaluate sesamin's binding affinity with the target proteins PPAR-γ and p21.

RESULTS: Sesamin treatment significantly reduced the viability of DU145 cells in a dose-dependent manner. Flow cytometry revealed increased apoptosis and cell cycle arrest at the G1 phase. Western blot analysis showed upregulated expression of PPAR-γ and p21, while p53 expression remained largely unchanged. Molecular docking analysis demonstrated strong binding affinity of sesamin to PPAR-γ (LibDock score: 125.03) and p21 (LibDock score: 105.45), supporting its involvement in a p53-independent apoptotic mechanism.

DISCUSSION: The study demonstrates that sesamin exerts significant anticancer effects on prostate cancer DU145 cells by inhibiting cell viability, inducing apoptosis, and causing G1 phase cell cycle arrest. The upregulation of PPAR-γ and p21, coupled with unchanged p53 expression, suggests that sesamin may activate a p53-independent pathway, a valuable feature in treating prostate cancers with defective p53 signaling. Molecular docking results corroborate these findings, indicating direct interactions between sesamin and its molecular targets.

CONCLUSION: Sesamin exhibits promising antiproliferative and pro-apoptotic activities against DU145 prostate cancer cells. Its potential to act as a G1-phase-specific chemotherapeutic agent via a p53-independent mechanism warrants further investigation and development as a natural candidate for prostate cancer therapy.