Mitochondria-Mediated Anticancer Effects of Two Previously Characterized Cox-2 Inhibitors in Hepatocellular Carcinoma Publisher Pubmed



Mirzaei R ; Varkiani M M ; Moosavi M ; Habibi R ; Niknam F ; Movahed M A ; Zarghi A ; Pourahmad J
Source: Molecular and Cellular Biochemistry Published:2026

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and often shows limited response to current therapies like sorafenib. This study investigates the selective anticancer activity and mitochondria-mediated apoptotic effects of two previously characterized COX-2 inhibitors, ZMA-M3 (imidazo[1,2-a]pyrazine) and ZMA-M4 (imidazo[1,2-a]pyridine), in isolated HCC and normal rat hepatocytes. Isolated HCC and normal rat hepatocytes were treated with various concentrations of ZMA-M3 and ZMA-M4 to determine their half-maximal inhibitory concentrations (IC50). Apoptosis was evaluated using Annexin V-FITC/PI staining and caspase-3 activity assays. Mitochondrial dysfunction was assessed by measuring reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release. Isolated HCC and normal rat hepatocytes were treated with various concentrations of ZMA-M3 and ZMA-M4 to determine their half-maximal inhibitory concentrations (IC50). Apoptosis was evaluated using Annexin V-FITC/PI staining and caspase-3 activity assays. Mitochondrial dysfunction was assessed by measuring reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026.