Molecular mechanisms of leptin and pro-apoptotic signals induced by menadione in HepG2 cells

Apoptosis is a significant physiological function in the cell. P⁵³ is known as tumor suppressor cellular factor, executive caspases are also the most involved pathway for apoptosis. Menadione (VK3) has apoptotic action on many harmful cells, but the molecular role of adipokines is not studied enough in this regard, so the ability of menadione to modify the adipokine (leptin hormone), caspase-3 and P⁵³ signals to induce its apoptotic action on HepG2 cells was studied. The study revealed that menadione has anti-viability and apoptotic effect at sub-G1 phase of HepG2 cell cycle. Its cytotoxic effect is mediated by molecular mechanisms included: inhibiting leptin expression and level, activating caspase-3 pathway and up-regulating the expression of P⁵³. Menadione exerts its apoptotic mechanisms in a concentration and time dependent way through ROS generation. In addition to the known apoptotic pathways, the results indicate that suppressing leptin pathway is a significant mechanism for menadione apoptotic effect which made it as a potential therapeutic vitamin in preventing hepatocyte survival and proliferation.