Oleanolic Acid Induces Metabolic Adaptation in Cancer Cells by Activating the AMP-Activated Protein Kinase Pathway
Oleanolic Acid Induces Metabolic Adaptation in Cancer Cells by Activating the AMP-Activated Protein Kinase Pathway
复制标题
齐墩果酸通过激活 AMP 激活的蛋白激酶途径诱导癌细胞的代谢适应
DOI：
10.1021/jf500622p
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发表时间：
2014-06-18
影响因子：
6.1
通讯作者：
Lin, Xiukun
中科院分区：
文献类型：
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作者：
Liu, Jia;Zheng, Lanhong;Lin, Xiukun
众所周知，癌细胞需要通过改变代谢来持续供应蛋白质、脂质、RNA和DNA以加速细胞增殖。因此，靶向代谢途径是一种有前途的癌症治疗策略。油酸（OA）广泛存在于食用和药用植物中，主要通过诱导细胞凋亡和细胞周期阻滞对癌细胞显示出选择性细胞毒性。本研究探讨OA是否通过影响肿瘤细胞的代谢来抑制肿瘤细胞的生长。OA被发现激活AMP激活蛋白激酶（AMPK），代谢的主要调节剂，在前列腺癌细胞系PC-3和乳腺癌细胞系MCF-7。AMPK活化是OA对癌细胞的抗肿瘤活性所必需的。脂肪生成，蛋白质合成，有氧糖酵解与OA治疗的癌细胞中，在AMPK激活依赖性的方式受到抑制。代谢改变被证明介导OA对癌细胞的肿瘤抑制活性。总的来说，这项研究提供了证据表明，OA作为一种广泛分布的营养成分，能够通过干扰癌细胞的代谢途径发挥抗肿瘤功能。这一发现应该鼓励研究人员研究影响癌症代谢是否是营养化合物抑制癌症的常见机制。
Cancer cells are well-known to require a constant supply of protein, lipid, RNA, and DNA via altered metabolism for accelerated cell proliferation. Targeting metabolic pathways is, therefore, a promising therapeutic strategy for cancers. Oleanolic acid (OA) is widely distributed in dietary and medicinal plants and displays a selective cytotoxicity to cancer cells, primarily by inducing apoptosis and cell cycle arrest. This study investigated if OA inhibited growth of tumor cells by affecting their metabolism. OA was found to activate AMP-activated protein kinase (AMPK), the master regulator of metabolism, in prostate cancer cell line PC-3 and breast cancer cell line MCF-7. AMPK activation is required for the antitumor activity of OA on cancer cells. Lipogenesis, protein synthesis, and aerobic glycolysis were inhibited in cancer cells treated with OA, in an AMPK activation-dependent manner. The metabolic alteration was shown to mediate the tumor suppressor activity of OA on cancer cells. Collectively, this study provides evidence that OA, as a widely distributed nutritional component, is able to exert antitumor function by interfering in the metabolic pathway in cancer cells. This finding should encourage researchers to study if affecting cancer metabolism is a common mechanism by which nutritional compounds suppress cancers.