Xanthatin inhibits human colon cancer cells progression via mTOR signaling mediated energy metabolism alteration
Xanthatin inhibits human colon cancer cells progression via mTOR signaling mediated energy metabolism alteration
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黄黄素通过 mTOR 信号介导的能量代谢改变抑制人结肠癌细胞的进展
DOI：
10.1002/ddr.21850
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发表时间：
2021-06
影响因子：
3.8
通讯作者：
Zhang Lei
中科院分区：
文献类型：
--
作者：
Li Lingli;Liu Ping;Xie Yanbo;Liu Yunxiao;Chen Zhaolin;Geng Yadi;Zhang Lei
肿瘤细胞表现出较高的糖酵解，并依靠异常的能量代谢产生ATP，这是细胞增殖和迁移所必需的。异常能量代谢抑制被认为是一种很有前途的肿瘤治疗策略。黄嘌呤是一种从苍耳菌中分离得到的活性倍半萜内酯。本研究评价了黄嘌呤对结肠癌细胞能量代谢的影响。结果表明，黄原素显著抑制人HT‐29和HCT‐116结肠癌细胞的迁移和侵袭。我们发现黄原素有效地减少了ATP的产生，促进了乳酸的积累。黄嘌呤抑制糖酵解可能与葡萄糖转运蛋白1 （Glut1）和单羧酸转运蛋白4 (MCT4) mRNA和蛋白水平的降低有关。同时，黄原素促进复合物II活性和氧化磷酸化（OXPHOS），导致HT‐29细胞线粒体损伤和细胞死亡。此外，黄嘌呤抑制HT - 29细胞中mTOR、4E结合蛋白1 （4E - BP1）和c - myc的磷酸化。此外，mTOR抑制剂雷帕霉素可以增强黄嘌呤处理的HT‐29细胞的细胞毒性作用。此外，转染si - mTOR的HT - 29细胞加重了黄嘌呤诱导的细胞活力抑制。基于这些结果，我们观察到黄原素对能量代谢的影响可能与其抑制mTOR信号通路有关。综上所述，本研究对黄嘌呤的抗癌作用提供了重要的见解，黄嘌呤通过调节人类结肠癌细胞的能量代谢而发生抗癌作用，并提示黄嘌呤有潜力作为一种植物性药物来对抗异常的肿瘤能量代谢。
Tumor cells exhibit higher glycolysis and rely on abnormal energy metabolism to produce ATP, which is essential for cell proliferation and migration. Abnormal energy metabolism inhibition is considered a promising tumor treatment strategy. Xanthatin is an active sesquiterpene lactone isolated from Xanthium strumarium L. This study evaluated the effect of xanthatin on the energy metabolism of human colon cancer cells. The results showed that xanthatin significantly inhibited the migration and invasion of human HT‐29 and HCT‐116 colon cancer cells. We found that xanthatin effectively reduced the production of ATP and promoted the accumulation of lactate. Xanthatin inhibited glycolysis which may be related to the reduction of glucose transporter 1 (Glut1) and monocarboxylate transporter 4 (MCT4) mRNA and protein levels. Concomitantly, xanthatin promoted complex II activity and oxidative phosphorylation (OXPHOS), resulting in mitochondrial damage and cell death in HT‐29 cells. Furthermore, xanthatin inhibited the phosphorylation of mTOR, the phosphorylation of 4E‐binding protein 1 (4E‐BP1) and c‐myc in HT‐29 cells. Moreover, rapamycin, a mTOR inhibitor, could enhance the cytotoxicity effect in xanthatin treated HT‐29 cells. Additionally, HT‐29 cells transfected with si‐mTOR aggravated xanthatin induced cell viability inhibition. Based on these results, we observed that the effect of xanthatin on energy metabolism may be related to its inhibition of the mTOR signaling pathway. Collectively, this study provides important insights into xanthatin's anticancer effect, which occurs by regulation of the energy metabolism of human colon cancer cells, and suggest that xanthatin has potential as a botanical drug against abnormal tumor energy metabolism.
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影响因子：
29
作者：
Pavlova NN;Thompson CB
通讯作者：
Thompson CB
明智地切换MTOR活动以打击胰岛素抵抗和癌症：当前的证据和观点。
影响因子：
5.6
作者：
Ong PS;Wang LZ;Dai X;Tseng SH;Loo SJ;Sethi G
通讯作者：
Sethi G
DOI：
10.14694/edbk_175561
发表时间：
2017-01-01
期刊：
American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
影响因子：
--
作者：
Weyandt, Jamie D;Thompson, Craig B;Rathmell, W Kimryn
通讯作者：
Rathmell, W Kimryn
影响因子：
3.1
作者：
Singh, DH;Banerji, AK;Jain, V
通讯作者：
Jain, V
GLUT1 调节前列腺癌中的细胞糖酵解和增殖
影响因子：
2.8
作者：
Xiao, Hengjun;Wang, Jun;Chen, Jun
通讯作者：
Chen, Jun