Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui, China.
Drug Dev Res. 2022 Aug;83(5):1176-1189. doi: 10.1002/ddr.21941. Epub 2022 Apr 24.
Lung cancer is the cancer with the highest mortality, and non-small cell lung cancer (NSCLC) accounts for more than 80%. Tumor cells often have high reactive oxygen species (ROS) and antioxidant capacity. Redox balance is very important for tumor. The decline of antioxidant capacity and excessive ROS will induce the death of tumor cells. Destroying the redox balance of tumor cells is a promising tumor treatment strategy. Xanthatin is an active sesquiterpene lactone isolated from Xanthium strumarium L. We observed that xanthatin induced the up regulation of mitochondrial ROS and mitochondrial damage. Meanwhile, our results showed that xanthatin could inhibit system x and reduce glutathione (GSH) synthesis. Antioxidant GSH and N-acetyl- l-cysteine (NAC) significantly reversed cell proliferation inhibition and apoptosis induced by xanthatin. β-Mercaptoethanol (β-ME) which can avoid inhibition of system x can also reverse the inhibition of cell proliferation induced by xanthatin, si-SLC7A11 was the opposite. Based on these results, we believe that the inhibition of xanthatin on the proliferation of NSCLC cells may be related to breaking the intracellular redox balance. Our data suggest that xanthatin is a promising antitumor candidate for the treatment of NSCLC.
肺癌是死亡率最高的癌症，其中非小细胞肺癌（NSCLC）占比超过 80%。肿瘤细胞通常具有较高的活性氧物种（ROS）和抗氧化能力。氧化还原平衡对肿瘤非常重要。抗氧化能力的下降和过量的 ROS 会诱导肿瘤细胞死亡。破坏肿瘤细胞的氧化还原平衡是一种有前途的肿瘤治疗策略。茵陈色原酮是从茵陈蒿中分离得到的一种活性倍半萜内酯。我们观察到茵陈色原酮诱导线粒体 ROS 的上调和线粒体损伤。同时，我们的结果表明，茵陈色原酮可以抑制系统 x 并减少谷胱甘肽（GSH）的合成。抗氧化剂 GSH 和 N-乙酰-l-半胱氨酸（NAC）可显著逆转茵陈色原酮诱导的细胞增殖抑制和凋亡。可以避免抑制系统 x 的β-巯基乙醇（β-ME）也可以逆转茵陈色原酮诱导的细胞增殖抑制，si-SLC7A11 的作用则相反。基于这些结果，我们认为茵陈色原酮对 NSCLC 细胞增殖的抑制可能与打破细胞内氧化还原平衡有关。我们的数据表明，茵陈色原酮是治疗 NSCLC 的一种很有前途的抗肿瘤候选药物。
