Liu Ning, Li Yongxi, Chen Guanzhi, Ge Keli
Department of Dermatology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong 266011, P.R. China.
Department of Dermatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
Oncol Lett. 2020 Oct;20(4):121. doi: 10.3892/ol.2020.11983. Epub 2020 Aug 13.
Melanoma is a common solid malignant tumor with a high frequency of metastasis and relapse. Evodiamine (EVO), a natural small molecule, has recently attracted considerable attention due to its pharmacological action, including its anticancer effects. However, the mechanism of the cytotoxic effect exerted by EVO on tumor cells is not yet fully understood. The present study aimed to evaluate the antitumor effects of evodiamine in human melanoma A-375 cells. The results demonstrated that EVO inhibited cell proliferation and induced cell cycle arrest at the G/M stage in human melanoma A-375 cells. The results also revealed that EVO exposure induced the activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase 1, as well as mitochondrial membrane potential dissipation in a time-dependent manner, indicating that EVO induced intrinsic apoptosis in A-375 cells. Furthermore, the results revealed that receptor-interacting serine/threonine kinase (RIP) and RIP3 were sequentially activated, suggesting that necroptosis may also be involved in EVO-induced cell death in A-375 cells. In addition, co-treatment with catalase was demonstrated to significantly attenuate the EVO-induced cell death in A-375 cells, indicating that reactive oxygen species (ROS) may serve an important role in EVO-induced cell death. In conclusion, the results of the present study unveiled a novel mechanism of drug action by EVO in human melanoma cells and suggested its potential value in treating human melanoma by inducing cell death via ROS activation.
黑色素瘤是一种常见的实体恶性肿瘤，转移和复发频率较高。吴茱萸碱（EVO）是一种天然小分子，因其药理作用，包括抗癌作用，最近受到了相当多的关注。然而，EVO对肿瘤细胞产生细胞毒性作用的机制尚未完全明确。本研究旨在评估吴茱萸碱对人黑色素瘤A-375细胞的抗肿瘤作用。结果表明，EVO抑制人黑色素瘤A-375细胞的增殖，并诱导细胞周期停滞于G/M期。结果还显示，EVO处理以时间依赖性方式诱导半胱天冬酶-3、半胱天冬酶-9和聚（ADP-核糖）聚合酶1的激活，以及线粒体膜电位的消散，表明EVO诱导A-375细胞发生内源性凋亡。此外，结果显示受体相互作用丝氨酸/苏氨酸激酶（RIP）和RIP3被依次激活，提示坏死性凋亡可能也参与了EVO诱导的A-375细胞死亡。另外，过氧化氢酶联合处理被证明可显著减轻EVO诱导的A-375细胞死亡，表明活性氧（ROS）可能在EVO诱导的细胞死亡中起重要作用。总之，本研究结果揭示了EVO在人黑色素瘤细胞中的一种新的药物作用机制，并提示其通过激活ROS诱导细胞死亡在治疗人黑色素瘤方面的潜在价值。
