Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Shikonin in Colon Cancer.
Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Shikonin in Colon Cancer.
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DOI：
10.3389/fphar.2020.544647
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发表时间：
2020
影响因子：
5.6
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Chen Y;Gao Y;Yi X;Zhang J;Chen Z;Wu Y
结直肠癌是一种发生在消化系统的常见恶性肿瘤，是发达国家癌症死亡率的第三大常见原因。紫草素是一种从紫草根中提取的萘醌类化合物，被广泛报道对多种癌症具有抗肿瘤活性。然而，紫草素对结肠癌的系统性影响仍然知之甚少。在本研究中，我们评估了紫草素对人结肠癌细胞的抗肿瘤活性和对异种移植小鼠模型的治疗作用。转录组学和代谢组学进一步结合，为紫草素抗肿瘤机制提供了系统的视角。结果表明，紫草素在体内和体外均具有明显的抗肿瘤活性。此外，代谢途径，包括嘌呤代谢、氨基酸代谢和甘油磷脂代谢，受到干扰，随后导致细胞周期阻滞在G2/M期。特别是嘌呤代谢的紊乱可能是紫草素抗肿瘤作用的主要机制。
Colorectal cancer is a common malignancy occurring in the digestive system, which is the third common cause of cancer mortality in developed countries. Shikonin, a naphthoquinone compound extracted from the root of Lithospermum erythrorhizon, is extensively reported to exert antitumor activity against various types of cancer. However, the systematic effect of shikonin in colon cancer remains poorly understood. In the present study, we evaluated the antitumor activity of shikonin in human colon cancer cells and the therapeutic effect on a xenograft mouse model. Transcriptomics and metabolomics were further integrated to provide a systematic perspective of the shikonin-induced antitumor mechanism. The results demonstrated that shikonin had a remarkable antitumor potency both in vitro and in vivo. Moreover, metabolic pathways, including the purine metabolism, amino acid metabolism, and glycerophospholipid metabolism, were perturbed and subsequently led to cell cycle arrest in the G2/M phase. In particular, the disturbance of purine metabolism may account for the major mechanism resulting from shikonin antitumor activity.
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影响因子：
4.8
作者：
Bronder, JL;Moran, RG
通讯作者：
Moran, RG
影响因子：
8.8
作者：
Newman AC;Maddocks ODK
通讯作者：
Maddocks ODK
RIP1 自磷酸化由线粒体 ROS 促进，对于 RIP3 募集到坏死体至关重要
影响因子：
16.6
作者：
Zhang Y;Su SS;Zhao S;Yang Z;Zhong CQ;Chen X;Cai Q;Yang ZH;Huang D;Wu R;Han J
通讯作者：
Han J
DOI：
10.1016/j.neo.2018.07.006
发表时间：
2018-09
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Chakravarthi BVSK;Rodriguez Pena MDC;Agarwal S;Chandrashekar DS;Hodigere Balasubramanya SA;Jabboure FJ;Matoso A;Bivalacqua TJ;Rezaei K;Chaux A;Grizzle WE;Sonpavde G;Gordetsky J;Netto GJ;Varambally S
通讯作者：
Varambally S
DOI：
10.1038/nrg.2018.4
发表时间：
2018-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Karczewski KJ;Snyder MP
通讯作者：
Snyder MP