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提取物可诱导人结肠癌细胞系生长抑制及细胞周期调控分子蛋白表达的变化。

Extracts of induce growth inhibition and changes in the protein expression of cell cycle control molecules in human colorectal cancer cell lines.

作者信息

Matsumoto Harutoshi, Ando Saeko, Yoshimoto Eri, Numano Takamasa, Sultana Nahida, Fukamachi Katsumi, Iinuma Munekazu, Okuda Kensuke, Kimura Kazunori, Suzui Masumi

机构信息

Department of Neurotoxicology, Graduate School of Medical Sciences and Medical School, Nagoya City University, Nagoya, Aichi 467-8601, Japan.

Department of Clinical Pharmaceutics, Graduate School of Medical Sciences and Medical School, Nagoya City University, Nagoya, Aichi 467-8601, Japan.

出版信息

Oncol Lett. 2022 Mar;23(3):99. doi: 10.3892/ol.2022.13219. Epub 2022 Jan 27.

DOI:10.3892/ol.2022.13219
PMID:35154430
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8822496/
Abstract

(MB) is a species of the banana plant belonging to the genus that has been used as a folk medicine. However, evidence-based biological activities and the molecular mechanism of action of MB are unknown. Thus, the aim of the present study was to examine whether the crude dried leaf extracts of MB inhibit the growth of colorectal (HT29 and HCT116) and other types (HepG2, MCF-7 and PC-3) of human cancer cell lines. Crude extracts of MB inhibited the growth of cells with IC values of 136 µg/ml (acetone extract, HT29), 51 µg/ml (acetone extract, HCT116), 45 µg/ml (acetone extract, HepG2), 40 µg/ml (acetone extract, MCF-7), 29 µg/ml (acetone extract, PC-3), 175 µg/ml (methanol extract, HT29), 137 µg/ml (methanol extract, HCT116), 102 µg/ml (methanol extract, HepG2), 85 µg/ml (methanol extract, MCF-7), and 85 µg/ml (methanol extract, PC-3) in colony formation assays, and 126 µg/ml (acetone extract, HT29), 68 µg/ml (acetone extract, HCT116), 260 µg/ml (methanol extract, HT29), and 216 µg/ml (methanol extract, HCT116) in MTT assays. Thin layer chromatography analysis revealed the potential existence of aromatic compounds in the acetone extract of MB. Flow cytometric analysis indicated that the percentage of cells in G1 increased, and this was associated with a concomitant decrease of cells in the S and/or G2-M phases of the cell cycle. When colorectal cancer cells were treated with acetone extract of MB, there was a marked decrease in the levels of expression of the cyclin D1, cyclin E, cdk2 and cdk4 proteins and a marked increase in the levels of the expression of the p21, p27, and p53 proteins, but those of apoptosis-associated protein PARP did not change. There was a tendency for acetone extract of MB to inhibit xenograft tumor growth in mice. Collectively, the crude extracts of MB contain active components that exert growth inhibition of human cancer cells. This is the first systematic study of the anticancer activity of MB and may broaden insights into the possible clinical approach of specific herbal medicines.

摘要

(MB)是香蕉属的一种植物,一直被用作民间药物。然而,MB基于证据的生物活性和作用分子机制尚不清楚。因此,本研究的目的是检测MB的粗制干叶提取物是否能抑制结肠直肠癌(HT29和HCT116)及其他类型(HepG2、MCF - 7和PC - 3)的人癌细胞系的生长。MB的粗提取物在集落形成试验中抑制细胞生长的IC值分别为:136 µg/ml(丙酮提取物,HT29)、51 µg/ml(丙酮提取物,HCT116)、45 µg/ml(丙酮提取物,HepG2)、40 µg/ml(丙酮提取物,MCF - 7)、29 µg/ml(丙酮提取物,PC - 3)、175 µg/ml(甲醇提取物,HT29)、137 µg/ml(甲醇提取物,HCT116)、102 µg/ml(甲醇提取物,HepG2)、85 µg/ml(甲醇提取物,MCF - 7)和85 µg/ml(甲醇提取物,PC - 3);在MTT试验中分别为:126 µg/ml(丙酮提取物,HT29)、68 µg/ml(丙酮提取物,HCT116)、260 µg/ml(甲醇提取物,HT29)和216 µg/ml(甲醇提取物,HCT116)。薄层色谱分析显示MB的丙酮提取物中可能存在芳香族化合物。流式细胞术分析表明,G1期细胞百分比增加,这与细胞周期S期和/或G2 - M期细胞百分比的相应降低相关。当用MB的丙酮提取物处理结肠直肠癌细胞时,细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白依赖性激酶2(cdk2)和细胞周期蛋白依赖性激酶4(cdk4)蛋白的表达水平显著降低,而p21、p27和p53蛋白的表达水平显著增加,但凋亡相关蛋白PARP的表达水平没有变化。MB的丙酮提取物有抑制小鼠异种移植瘤生长的趋势。总体而言,MB的粗提取物含有对人癌细胞具有生长抑制作用的活性成分。这是对MB抗癌活性的首次系统性研究,可能会拓宽对特定草药可能的临床应用方法的认识。

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