¹Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ege University, 35040 İzmir, Turkey
²Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ondokuz Mayıs University, 55139 Samsun, Turkey
³Department of Pharmacognosy, Faculty of Pharmacy, Dicle University, 21830 Diyarbakır, Turkey
⁴Department of Pharmacognosy, Faculty of Pharmacy, Ege University, 35040 İzmir, Turkey
⁵Faculty of Pharmacy, Ege University, 35040 İzmir, Turkey DOI : 10.29228/jrp.874 Hepatocellular carcinoma is one of the most severe and life-threatening types of cancer. The conventional treatment of hepatoma has significant challenges due to the adverse effects of chemotherapy, leading to treatment failure and decreased survival. Therefore, developing and investigating novel and safer anticancer drugs and establishing more effective therapeutic regimens is a crucial field of research. The Haplophyllum megalanthum-derived compound matairesinol has demonstrated antiproliferative and antitumor activity against various types of cancer, including pancreatic, breast, and prostate cancer. However, the potential effects of matairesinol on liver cancer, as well as the underlying molecular mechanisms associated with its anticancer activity, have yet to be thoroughly elucidated. In the current study, we demonstrated that matairesinol inhibited the viability of human hepatoma cells in a dose-dependent manner. Besides, at IC50 and higher doses, matairesinol induced oxidative stress and impaired mitochondrial membrane potential and ATP levels, two evidence of mitochondrial damage. Moreover, matairesinol exposure led to significant caspase-3 activation, a hallmark of apoptosis. These results indicate that mitochondrial damage and caspase-3 activation may contribute to the cytotoxic effect of matairesinol on liver cancer cells. Keywords : Matairesinol; liver cancer; mitochondria; caspase-3; anticancer effect