The marine natural product, dicitrinone B, induces apoptosis through autophagy blockade in breast cancer.

Abstract

Being a highly conserved catabolic process, autophagy is induced by various forms of cellular stress, and its modulation has considerable potential as a cancer therapeutic approach. In the present study, it was demonstrated that dicitrinone B (DB), a rare carbon-bridged citrinin dimer, may exert anticancer effects by blocking autophagy at a late stage, without disrupting lysosomal function in MCF7 breast cancer and MDA-MB-231 triple-negative breast cancer cells. Furthermore, it was discovered that DB significantly enhanced intracellular reactive oxygen species (ROS) production and that the removal of ROS was followed by the attenuation of autophagy inhibition. In addition, DB exerted notable inhibitory effects on the proliferation and promoting effects on the apoptosis of MCF7 and MDA-MB-231 cells. In combination with conventional chemotherapeutic drugs, DB exhibited a further enhanced synergistic effect than when used as a single agent. Overall, the data of the present study demonstrate that DB may prove to be a promising autophagy inhibitor with anticancer activity against breast cancer.