Cytotoxic and anti-metastatic effects of Pllans-II from Porthidium lansbergii lansbergii venom against prostate cancer cells.

Prostate cancer remains a major health challenge due to therapeutic resistance and the adverse effects of conventional treatments. Snake venom phospholipases A have emerged as promising bioactive molecules with selective anti-cancer properties. In this study, we evaluated the cytotoxic and anti-metastatic effects of Pllans-II, an Asp-49 PLA purified from Porthidium lansbergii lansbergii venom, on prostate cancer cell lines. Pllans-II exerted a dose-dependent cytotoxic effect on LNCaP, PC-3, and DU-145 cells, with the strongest activity observed in LNCaP cells (IC = 100 μg/mL). In contrast, it spared non-tumorigenic prostate epithelial cells (PCS-440-010), unlike Docetaxel. Pllans-II did not compromise plasma membrane integrity, suggesting a non-lytic mechanism of action. Functional assays revealed that Pllans-II significantly inhibited LNCaP cell migration in both 2D wound-healing and 3D transwell models, reduced adhesion to fibronectin and Matrigel, and impaired clonogenic capacity. Western blot analysis revealed no change in the caspase-8 expression, but a marked upregulation of Beclin-1, probably related to autophagy cell death pathways. These findings highlight the selective cytotoxicity and anti-metastatic potential of Pllans-II, positioning it as a promising prototype for the development of novel therapeutic strategies against prostate cancer.