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芒果苷诱导A549人肺癌细胞凋亡和细胞周期阻滞的分子机制。

Molecular mechanisms underlying mangiferin-induced apoptosis and cell cycle arrest in A549 human lung carcinoma cells.

作者信息

Shi Wei, Deng Jiagang, Tong Rongsheng, Yang Yong, He Xia, Lv Jianzhen, Wang Hailian, Deng Shaoping, Qi Ping, Zhang Dingding, Wang Yi

机构信息

Department of Pediatrics, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.

Guangxi Province Key Laboratory, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P.R. China.

出版信息

Mol Med Rep. 2016 Apr;13(4):3423-32. doi: 10.3892/mmr.2016.4947. Epub 2016 Feb 29.

Abstract

Mangiferin, which is a C‑glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) purified from plant sources, has recently gained attention due to its various biological activities. The present study aimed to determine the apoptotic effects of mangiferin on A549 human lung adenocarcinoma cells. In vitro studies demonstrated that mangiferin exerted growth‑inhibitory and apoptosis-inducing effects against A549 cells. In addition, mangiferin exhibited anti-tumor properties in A549 xenograft mice in vivo. Mangiferin triggered G2/M phase cell cycle arrest via downregulating the cyclin-dependent kinase 1-cyclin B1 signaling pathway, and induced apoptotic cell death by inhibiting the protein kinase C-nuclear factor-κB pathway. In addition, mangiferin was able to enhance the antiproliferative effects of cisplatin on A549 cells, thus indicating the potential for a combined therapy. Notably, mangiferin exerted anticancer effects in vivo, where it was able to markedly decrease the volume and weight of subcutaneous tumor mass, and expand the lifespan of xenograft mice. The present study clarified the molecular mechanisms underlying mangiferin-induced antitumor activities, and suggested that mangiferin may be considered a potential antineoplastic drug for the future treatment of cancer.

摘要

芒果苷是一种从植物来源中纯化得到的C-葡萄糖基黄酮(1,3,6,7-四羟基黄酮-C2-β-D-葡萄糖苷),由于其多种生物活性,近年来受到关注。本研究旨在确定芒果苷对A549人肺腺癌细胞的凋亡作用。体外研究表明,芒果苷对A549细胞具有生长抑制和凋亡诱导作用。此外,芒果苷在A549异种移植小鼠体内表现出抗肿瘤特性。芒果苷通过下调细胞周期蛋白依赖性激酶1-细胞周期蛋白B1信号通路触发G2/M期细胞周期阻滞,并通过抑制蛋白激酶C-核因子-κB通路诱导凋亡性细胞死亡。此外,芒果苷能够增强顺铂对A549细胞的抗增殖作用,从而表明联合治疗的潜力。值得注意的是,芒果苷在体内发挥抗癌作用,能够显著减小皮下肿瘤块的体积和重量,并延长异种移植小鼠的寿命。本研究阐明了芒果苷诱导抗肿瘤活性的分子机制,并表明芒果苷可能被视为未来癌症治疗的潜在抗肿瘤药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af8/4805064/b1b8425b4ea8/MMR-13-04-3423-g00.jpg

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