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两种新型菲并吲哚里西啶生物碱化合物对人结肠癌细胞和肝癌细胞的体外抗癌作用

In vitro anticancer effects of two novel phenanthroindolizidine alkaloid compounds on human colon and liver cancer cells.

作者信息

Liu Jingjing, He Yu, Zhang Dan, Cai Ying, Zhang Chenggang, Zhang Peng, Zhu Hongxia, Xu Ningzhi, Liang Shufang

机构信息

Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.

Department of Chemistry and Materials, Sichuan Normal University, Chengdu, Sichuan 610066, P.R. China.

出版信息

Mol Med Rep. 2017 Sep;16(3):2595-2603. doi: 10.3892/mmr.2017.6879. Epub 2017 Jun 29.

Abstract

Malignant cancer is one of the most serious diseases threatening the health of human beings. Natural plant alkaloids exhibit multiple biological functions, including inhibition of cell proliferation, and may have potential anticancer activity. However, most natural alkaloids may not be suitable for human therapies owing to instability, poor dissolubility and potential side effects. To improve their anticancer activity and drug effect, the present study aimed to develop new alkaloid derivatives, the phenanthroindolizidine alkaloid compounds, and evaluated their potential antitumor effects on human cancer cells in vitro. Among the several newly synthesized analogues of phenanthroindolizidine alkaloids (PAs), the compounds YS306 and YS206 exhibited an increased growth inhibition activity on HepG2 liver cancer cells and on HCT116 and HT29 colon cancer cells, with half‑maximal inhibitory concentrations in the micromolar range. YS206 and YS306 (5 µg/ml) both significantly induced cell cycle arrest at the G2/M phase and notably decreased cell distribution at the G0/G1 and S phase. In addition, these two molecules significantly inhibited cancer cell migration, as analyzed by the wound‑healing and Transwell assays. However, neither YS306 nor YS206 exhibited observable effects on apoptosis. Therefore, chemical structure modifications of natural PAs based on anticancer activity assessments may be feasible in the development of new cancer chemotherapeutic agents.

摘要

恶性肿瘤是威胁人类健康的最严重疾病之一。天然植物生物碱具有多种生物学功能,包括抑制细胞增殖,可能具有潜在的抗癌活性。然而,由于稳定性差、溶解性低和潜在的副作用,大多数天然生物碱可能不适合用于人类治疗。为了提高其抗癌活性和药物效果,本研究旨在开发新的生物碱衍生物,即菲并吲哚里西啶生物碱化合物,并在体外评估它们对人类癌细胞的潜在抗肿瘤作用。在几种新合成的菲并吲哚里西啶生物碱(PAs)类似物中,化合物YS306和YS206对HepG2肝癌细胞以及HCT116和HT29结肠癌细胞表现出增强的生长抑制活性,半数最大抑制浓度在微摩尔范围内。YS206和YS306(5μg/ml)均显著诱导细胞周期停滞在G2/M期,并显著降低G0/G1期和S期的细胞分布。此外,通过伤口愈合试验和Transwell试验分析,这两种分子显著抑制癌细胞迁移。然而,YS306和YS206均未表现出对细胞凋亡的明显影响。因此,基于抗癌活性评估对天然PAs进行化学结构修饰在开发新的癌症化疗药物方面可能是可行的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be8/5548052/a97771e35521/MMR-16-03-2595-g00.jpg

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