Cytotoxic effects of epsilon toxin from Clostridium perfringens on colon cancer cell lines (HT-29) and (Caco2) in terms of oxidative stress and inflammatory cytokines

Bacterial toxins, such as Epsilon toxin (Etx) from Clostridium perfringens, represent a promising, albeit underexplored, avenue for anticancer agent development. This study was therefore designed to systematically investigate the cytotoxic mechanisms of Etx on the human colon cancer cell lines HT-29 and Caco-2. The primary focus was on the toxin's capacity to induce oxidative stress and pro-inflammatory responses, two key pathways in cancer pathology. Key parameters evaluated included cytotoxicity, ROS generation, lipid peroxidation, LDH release, and inflammatory cytokines (TNF-alpha and IL-6). The results demonstrated that treatment with Etx significantly inhibited the proliferation of both cell lines in a concentration-dependent manner, reducing cell viability by approximately 60% at the highest concentration. This cytotoxic effect was linked to a substantial increase in intracellular ROS and lipid peroxidation, confirming the induction of severe oxidative damage. Concurrently, Etx compromised cell membrane integrity, as evidenced by a marked increase in LDH release. Furthermore, the toxin fostered a potent pro-inflammatory environment by upregulating key cytokines. These findings collectively demonstrate that Etx exerts its potent cytotoxicity on colon cancer cells by concurrently triggering oxidative stress and a robust inflammatory cascade. This dual-mechanism of action highlights the potential of Etx as a novel therapeutic candidate, warranting further investigation into targeted delivery systems to translate its efficacy into clinical applications.