<i>Pllans−II</i>: Unveiling the Action Mechanism of a Promising Chemotherapeutic Agent Targeting Cervical Cancer Cell Adhesion and Survival Pathways

Abstract

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient’s quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans−II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, has shown selective attack against the HeLa and Ca Ski cervical cancer cell lines. This work suggests that the cytotoxic effect generated by Pllans−II on HeLa cells is triggered without affecting the integrity of the cytoplasmic membrane or depolarizing the mitochondrial membranes. The results allow us to establish that cell death in HeLa is related to the junction blockage between α5β1 integrins and fibronectin of the extracellular matrix. Pllans−II reduces the cells’ ability of adhesion and affects survival and proliferation pathways mediated by intracellular communication with the external environment. Our findings confirmed Pllans−II as a potential prototype for developing a selective chemotherapeutic drug against cervical cancer.

Keywords

• snake venom
• phospholipase A₂
• bioprospecting
• antitumor potential
• transcriptomic analysis
• membrane receptor target