Background Hepatocellular carcinoma (HCC) is an aggressive and common liver cancer with high recurrence and late‐stage diagnosis. Despite multiple treatment options, their effectiveness is limited, especially in advanced stages. Hepatocellular cancer cells show elevated oxidative stress, which can be targeted therapeutically. Pharmacological ascorbate (P‐AscH − ) and methylseleninic acid (MSA) are redox‐active agents that are selectively cytotoxic to cancer cells by increasing reactive oxygen species (ROS) generation. However, the therapeutic potential of new redox‐active agents in HCC is still poorly investigated. Methods HepG2 and THLE‐3 cells were treated with increasing concentrations of P‐AscH − (0–20 mM), MSA (0–40 µM), or a combination of both. Cell viability was assessed using the MTS assay. ROS levels, particularly hydroxyl radicals, were measured using the OH580 fluorescent probe. Catalase (CAT) activity and concentration were quantified via a colorimetric assay and ELISA, respectively. Results P‐AscH − and MSA each induced dose‐dependent cytotoxicity in HepG2 cells without significantly affecting THLE‐3 normal liver cells. The combination treatment exhibited enhanced cytotoxicity in HepG2 cells, suggesting synergistic effects. ROS analysis revealed increased hydroxyl radical production in the combination group. Furthermore, CAT activity and expression were significantly altered in HepG2 cells treated with both agents, indicating impaired antioxidant defense and enhanced oxidative damage. Conclusion The combination of P‐AscH − and MSA selectively enhances cytotoxicity in HCC cells by increasing oxidative stress and suppressing CAT activity. These findings support further exploration of this combinatory approach as a potential therapeutic strategy for HCC.
Rataan et al. (Thu,) studied this question.