Dimethoxytolyl propylresorcinol induces apoptosis and mitophagy in human leukemia cells through the PI3K/AKT pathway

Dimethoxytolyl propylresorcinol (UP302), a natural compound extracted from Dianella ensifolia, owing to its tyrosinase inhibitory and strong antioxidant properties, is used in whitening cosmetics. However, the role of UP302 has not been reported in cancer treatment. This study aimed to assess the in vitro antitumor activity of UP302 in different tumor cells. It inhibited the growth of certain cancer cell lines and especially in leukemia cells. Therefore, we investigated the antitumor effect of UP302 in leukemia by examining the cell cycle, apoptosis, reactive oxygen species levels (ROS) production, and changes in mitochondrial membrane potential. Our results demonstrated that UP302 inhibited the growth of leukemia cells both in vivo and in vitro and exerted a proapoptotic effect on MV411 and K562 cells, confirmed by flow cytometry and western blot analysis. Furthermore, UP302 promoted autophagy in MV411 and K562 cells. Transmission electron microscopy and western blot analysis showed that UP302 induced mitophagy in MV411 and K562 cells. In addition, the autophagy inhibitor chloroquine could enhance UP302-induced apoptosis, suggesting that UP302-mediated autophagy may be protective in MV411 and K562 cells. In conclusion, our study is the first to provide evidence for the anti-leukemia properties of UP302 and the potential clinical use of UP302 combined with autophagy inhibitors as a chemotherapeutic strategy for human leukemia.