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芹菜素在体外抑制口腔鳞状细胞癌生长,诱导细胞周期停滞和细胞凋亡。

Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis.

机构信息

Department of Surgery and Translational Medicine, University of Milan-Bicocca, I-20900 Monza, Italy.

出版信息

Int J Oncol. 2013 Nov;43(5):1675-82. doi: 10.3892/ijo.2013.2072. Epub 2013 Aug 21.

DOI:10.3892/ijo.2013.2072
PMID:23969487
Abstract

In the present study, we investigated the effect of apigenin, a flavonoid widely present in fruits and vegetables, on a tongue oral cancer-derived cell line (SCC-25) and on a keratinocyte cell line (HaCaT), with the aim of unveiling its antiproliferative mechanisms. The effect of apigenin on cell growth was evaluated by MTT assay, while apoptosis was investigated by phosphatidyl serine membrane translocation and cell cycle distribution by propidium iodide DNA staining through flow cytometry. In addition the expression of cyclins and cyclin-dependent kinases was evaluated by western blotting. A reduction of apigenin-induced cell growth was found in both cell lines, although SCC-25 cells were significantly more sensitive than the immortalized keratinocytes, HaCaT. Moreover, apigenin induced apoptosis and modulated the cell cycle in SCC-25 cells. Apigenin treatment resulted in cell cycle arrest at both G0/G1 and G2/M checkpoints, while western blot analysis revealed the decreased expression of cyclin D1 and E, and inactivation of CDK1 upon apigenin treatment. These results demonstrate the anticancer potential of apigenin in an oral squamous cell carcinoma cell line, suggesting that it may be a very promising chemopreventive agent due to its cancer cell cytotoxic activity and its ability to act as a cell cycle modulating agent at multiple levels.

摘要

在本研究中,我们研究了广泛存在于水果和蔬菜中的类黄酮芹菜素对舌口腔癌细胞系(SCC-25)和角质形成细胞系(HaCaT)的影响,旨在揭示其抗增殖机制。通过 MTT 测定法评估了芹菜素对细胞生长的影响,通过流式细胞术通过碘化丙啶 DNA 染色研究了膜转位和细胞周期分布的细胞凋亡。此外,通过蛋白质印迹法评估了细胞周期蛋白和细胞周期蛋白依赖性激酶的表达。发现两种细胞系中的芹菜素诱导的细胞生长均减少,尽管 SCC-25 细胞比永生化角质形成细胞 HaCaT 敏感得多。此外,芹菜素诱导 SCC-25 细胞凋亡并调节细胞周期。芹菜素处理导致细胞周期在 G0/G1 和 G2/M 检查点停滞,而 Western blot 分析显示芹菜素处理后细胞周期蛋白 D1 和 E 的表达减少,以及 CDK1 的失活。这些结果表明,在口腔鳞状细胞癌细胞系中,芹菜素具有抗癌潜力,表明由于其癌细胞细胞毒性活性及其作为多个水平的细胞周期调节因子的能力,它可能是一种非常有前途的化学预防剂。

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