Abstract
Ferroptosis, 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.
Highlights
Lung cancer is the most common cause of cancer death around the world.[1]
Our results suggest that the natural product erianin exerts its anticancer effects by inducing calcium/calmodulin-dependent ferroptosis and inhibiting metastasis in lung cancer cells
Cell counting kit-8 (CCK-8) assays showed that erianin increased the inhibition of the growth of lung cancer cells (Fig. 1a, b)
Summary
Lung cancer is the most common cause of cancer death around the world.[1] Surgery is still the key approach used for lung cancer therapy; a large number of patients die due to recurrence and drug treatment failure.[2] Despite recent advances in the development of new chemotherapeutic agents, molecularly targeted drugs, and antibodies that block immune checkpoints, many obstacles remain.[3,4] identifying new anticancer strategies besides chemotherapy, radiation, and immunotherapy will be critical if we hope to improve cure rates for patients with advanced lung cancer. A natural product isolated from Dendrobium chrysotoxum. Lindl, has been reported to exert antitumor effects on several cancer types. Wang et al.[5] demonstrated that erianin could be a promising drug for the treatment of osteosarcoma, as it induced G2/M cell cycle arrest and triggered cell death via the ROS/JNK signaling pathway
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