Menthol induces extracellular vesicle regulation of apoptosis via ATG3 and caspase-3 in acute leukemic cells

Leukemia is one of the most deadly cancers in Thailand. Natural compounds have been developed for cancer treatment. Menthol, a peppermint compound, has shown pharmacological properties such as anti-cancer activity. However, the mechanism of menthol inducing extracellular vesicles in leukemic cells is not yet understood. In this study, we investigated the effects of menthol on leukemic extracellular vesicles and their role in apoptosis. NB4 and Molt-4 leukemic cells were cultured with menthol in various concentrations and times. Bioinformatic analysis was used to investigate target proteins of extracellular vesicle and apoptosis, followed by mRNA and protein expression by RT‒PCR and western blotting, respectively. Our findings indicate that menthol inhibits leukemic cell proliferation and increases extracellular vesicles. Furthermore, menthol treated leukemic extracellular vesicles induce apoptosis and upregulate the expression of ATG3 and caspase-3 in both mRNA and protein levels. These results suggest that menthol has an antileukemic effect through ATG3 and caspase-3 in apoptosis of leukemic extracellular vesicles.