Temozolomide-perillyl alcohol conjugate induced reactive oxygen species accumulation contributes to its cytotoxicity against non-small cell lung cancer.
Temozolomide-perillyl alcohol conjugate induced reactive oxygen species accumulation contributes to its cytotoxicity against non-small cell lung cancer.
复制标题
替莫唑胺-紫苏醇缀合物诱导的活性氧积累有助于其对抗非小细胞肺癌的细胞毒性。
DOI：
10.1038/srep22762
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发表时间：
2016-03-07
影响因子：
4.6
通讯作者：
Song X
中科院分区：
文献类型：
--
作者：
Song X;Xie L;Wang X;Zeng Q;Chen TC;Wang W;Song X
替莫唑胺-紫苏醇结合物(TmZ- − -POH)是一种新的替莫唑胺类似物，据报道在三阴性乳腺癌和耐药胶质瘤中具有细胞毒作用。在目前的一项研究中，我们展示了TMZ − POH对最常见的肺癌类型非小细胞肺癌的细胞毒性，从细胞/肿瘤增殖抑制、G2/M期阻滞、DNA损伤和线粒体凋亡等方面证明了这一点。重要的是，TMZ − POH的细胞毒性与ROS的积累密切相关，因为它可以被两种ROS清除剂过氧化氢酶(CAT)和N-乙酰-L-半胱氨酸(NAc)逆转。TMZ − POH诱导线粒体跨膜电位降低和ROS积聚，进而激活丝裂原活化蛋白激酶(MAPKs)信号转导和线粒体凋亡，从而发挥其细胞毒作用，提示TMZ − POH有可能成为治疗非小细胞肺癌的候选药物。
Temozolomide-perillyl alcohol conjugate (TMZ − POH), a novel temozolomide analog, was reported to play a cytotoxic role in triple-negative breast cancer and TMZ-resistant gliomas. In a current study we had demonstrated how TMZ − POH also exhibited its cytotoxicity against non-small cell lung cancer (NSCLC), the most common type of lung cancer, as evidence from cell/tumor proliferation inhibition, G2/M arrest, DNA damage and mitochondrial apoptosis. Importantly, TMZ − POH’s cytotoxicity is closely related to reactive oxygen species (ROS) accumulation because it can be reversed by two ROS scavengers, catalase (CAT) and N-acetyl-L-cysteine (NAC). TMZ − POH induces mitochondrial transmembrane potential (MTP) decrease and ROS accumulation, in turn activates mitogen-activated protein kinase (MAPKs) signaling and mitochondrial apoptosis, and then exerts its cytotoxicity, thus proposing TMZ − POH as a potential therapeutic candidate for NSCLC.