Resorcinol alleviates alpha-terpineol-induced cell death in Schizosaccharomyces pombe via increased activity of the antioxidant enzyme Sod2.

Alpha-terpineol, popular monoterpenoid alcohol, is known to cause cytotoxicity in a few cancer cells or to have antioxidant activity, but underlying mechanisms or apoptotic processes in yeast cell death should be understood. We used the fission yeast (Schizosaccharomyces pombe) as a unicellular model to monitor cellular toxicology and physiological mechanisms for the involvement of alpha-terpineol in cell death. Alpha-terpineol caused Reactive oxygen species (ROS) overproduction and following cytotoxicity and apoptosis in a dose-dependent manner. The effect of oxidative stress was proved using sod1 and sod2 mutants (antioxidant-limited cells), and the results showed that apoptosis was caused by alpha-terpineol-driven oxidation. In addition, resorcinol, a herbal extract from medicinal plants, showed protective activity against alpha-terpineol cytotoxicity. Survival rates, apoptotic cell death ratios, oxidation levels, and antioxidant gene expressions were completely altered; surprisingly sod1 and sod2 levels dramatically increased. However, sod2 was highly upregulated in response to resorcinol treatment with alpha-terpineol. The potential role of the Sod2 enzyme was proved using sod2 mutant cells that do not have a mitochondrial radical-clearing activity. Consequently, the dose-dependent and ROS-mediated cytotoxic/apoptotic effects of alpha-terpineol and the Sod2-dependent protective and antioxidant effects of resorcinol were demonstrated in unicellular model organism S. pombe by this study.