A new therapeutic strategy for luminal A-breast cancer treatment: vulpinic acid as an anti-neoplastic agent induces ferroptosis and apoptosis mechanisms.

Abstract

Breast cancer is a common invasive tumor in women, and the most common subtype of breast cancer is luminal A. Hormonal therapies are the primary treatment for luminal A, but treatment options are limited. Vulpinic acid (VA), a lichen compound, inhibited cancer cells. Here, we aimed to reveal the functional role and mechanism of VA in luminal A breast cancer. Experiments associated with the ferroptosis mechanism were performed to reveal the role of vulpinic acid on luminal A-breast cancer and the underlying mechanisms. The results showed that VA induced the ferroptosis pathway by decreasing glutathione (GSH) levels while increasing lipid reactive oxygen species (ROS), lipid peroxidation (MDA), and intracellular Fe2+ levels in MCF-7 cells. After treatment of MCF-7 cells with VA, the ferroptosis-related gene expression profile was significantly altered. Western blot analysis showed that GPX4 protein levels were down-regulated and LPCAT3 protein levels were up-regulated after VA treatment. Our study suggests that apoptosis and ferroptosis act together in VA-mediated tumor suppression in MCF-7 breast cancer cells. These findings suggest that VA, an anti-neoplastic agent, could potentially treat luminal A targeted breast cancer via the ferroptosis pathway.