Work

Antiproliferative and apoptotic effects of (1R,12R)-dolabella-4(16),7,10-triene-3,13-dione (CI-A) in oral cancer cells are mediated by oxidative stress and ERK activation

Year: 2025

Type: article

Abstract: The anticancer effects and mechanisms of the main component (CI-A) of methanol extracts of Clavularia inflat have not been reported. This study explores the anti-oral cancer effect and mechanism of (1R*,12R*)-dolabella-4(16),7,10-triene-3,13-dione (CI-A) and compared with normal cells. CI-A shows oxidative-stress-dependent preferential antiproliferation of oral cancer cells without normal cell toxicity. CI-A triggers cell cycle dysregulation, apoptosis/caspase activation, cellular/mitochondrial ROS induction, glutathione depletion, and oxidative DNA damage in oral cancer but not normal cells. After testing with three MAPK (p38, JNK, and ERK) inhibitors, only the ERK inhibitor (PD98059) protects against CI-A-induced antiproliferation in oral cancer cells. CI-A upregulates phosphorylated ERK in oral cancer cells compared to normal cells. Notably, a ROS inhibitor, N-acetylcysteine (NAC), attenuates all CI-A-modulated changes. Moreover, the CI-A-triggered annexin V-detected apoptosis and caspase 3/8/9 activations of oral cancer cells were downregulated by PD98059. In conclusion, CI-A induces the oxidative-stress- and ERK-dependent antiproliferative and apoptotic mechanism in oral cancer cells and shows the benefit of non-cytotoxicity to normal cells.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.114615