Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis
Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis
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DOI：
10.1038/s41392-020-0149-3
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发表时间：
2020-05-08
影响因子：
39.3
通讯作者：
Sui, Xinbing
中科院分区：
文献类型：
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作者：
Chen, Peng;Wu, Qibiao;Sui, Xinbing
铁凋亡是一种新的程序性细胞死亡形式，其特征在于铁依赖性脂质过氧化，并已被证明与多种疾病有关，包括癌症。刺激癌细胞中的铁凋亡可能是癌症治疗的潜在策略。因此，铁中毒诱导药物在癌症治疗中越来越受到关注。在这里，我们表明毛兰素，从石斛分离的天然产物，发挥其抗癌活性，诱导细胞死亡和抑制肺癌细胞的细胞迁移。随后，我们首次证明毛兰素诱导肺癌细胞中的铁凋亡细胞死亡，这是伴随着ROS积累，脂质过氧化和GSH耗尽。铁凋亡抑制剂Fer-1和Lip-1而不是Z-VAD-FMK，CQ或necrostatin-1拯救了毛兰素诱导的细胞死亡，表明铁凋亡有助于毛兰素诱导的细胞死亡。此外，我们证明了Ca 2 +/CaM信号是毛兰素诱导的铁凋亡的关键介质，并且该信号的阻断通过抑制铁凋亡显著地挽救了毛兰素处理诱导的细胞死亡。综上所述，我们的数据表明，毛兰素发挥其抗肿瘤作用，诱导钙/钙调素依赖性铁凋亡和抑制细胞迁移，毛兰素有望成为一个有前途的化合物，用于肺癌治疗。
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.