Author:
Chen Peng,Wu Qibiao,Feng Jiao,Yan Lili,Sun Yitian,Liu Shuiping,Xiang Yu,Zhang Mingming,Pan Ting,Chen Xiaying,Duan Ting,Zhai Lijuan,Zhai Bingtao,Wang Wengang,Zhang Ruonan,Chen Bi,Han Xuemeng,Li Yicong,Chen Liuxi,Liu Ying,Huang Xingxing,Jin Ting,Zhang Wenzheng,Luo Hong,Chen Xiaohui,Li Yongqiang,Li Qiujie,Li Guohua,Zhang Qin,Zhuo Lvjia,Yang Zuyi,Tang Huifen,Xie Tian,Ouyang Xiaoping,Sui Xinbing
Abstract
AbstractFerroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases, including cancer. Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy. Therefore, ferroptosis-inducing drugs are attracting more attention for cancer treatment. Here, we showed that erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells. Subsequently, we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells, which was accompanied by ROS accumulation, lipid peroxidation, and GSH depletion. The ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK, CQ, or necrostatin-1 rescued erianin-induced cell death, indicating that ferroptosis contributed to erianin-induced cell death. Furthermore, we demonstrated that Ca2+/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis. Taken together, our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca2+/CaM-dependent ferroptosis and inhibiting cell migration, and erianin will hopefully serve as a prospective compound for lung cancer treatment.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC