Abstract
Ferroptosis is a recently identified form of programmed cell death that is iron-dependent and closely involved in the pathogenesis of breast cancer. Past studies have identified myricetin as being able to inhibit breast cancer growth through its targeting of apoptotic mechanisms, but the precise mechanisms whereby it exerts its antitumoral effects in breast cancer remain to be characterized in detail. Here, the effects of myricetin on the induction of ferroptosis in breast cancer cells were investigated. It was found that myricetin was able to significantly inhibit 4 T1 tumor cell viability and colony forming activity, increasing the level of MDA, Fe2+, and ROS within these cells. From a mechanistic perspective, myricetin was found to induce ferroptotic 4 T1 cell death via downregulating Nrf-2 and GPX4. In vivo experimentation demonstrated that myricetin treatment was sufficient to reduce the growth of subcutaneous breast tumors in female mice as evidenced by decreases in tumor weight and volume, while significantly inhibiting Nrf-2 and GPX4 expression within the tumors of treated mice. Myricetin is capable of readily suppressing breast tumor growth in mice via the induction of ferroptotic activity through the Nrf-2/GPX4 pathway. Myricetin may thus offer utility as a therapeutic agent for the management of breast cancer in clinical settings.