Chimplee Siriphorn, Graidist Potchanapond, Srisawat Theera, Sukrong Suchada, Bissanum Rassanee, Kanokwiroon Kanyanatt
Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
Oncol Lett. 2019 Jun;17(6):5283-5291. doi: 10.3892/ol.2019.10209. Epub 2019 Apr 3.
Breast cancer is the leading cause of female mortality worldwide. Although there are several modern treatments for breast cancer, there is a high rate of recurrence for the majority of treatments; therefore, the search for effective anticancer agents continues. The present study aimed to investigate the anti-breast cancer potential of frullanolide, a compound which is isolated and purified from the plant, for selected human breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). The MTT assay was used to assess cytotoxic activity in breast cancer cell lines of treatment with frullanolide at 1.25, 2.5, 5.0, 10.0 and 20.0 µg/ml. Additionally, the apoptotic induction ability of frullanolide at various concentrations [0.5×, 1× and 2× half maximal inhibitory concentration (IC)] was investigated by flow cytometry and western blot analysis. Frullanolide exhibited strong anti-breast cancer activity against MDA-MB-468 (IC, 8.04±2.69 µg/ml) and weak cytotoxicity against the MCF-7 (IC, 10.74±0.86 µg/ml) and MDA-MB-231 (IC, 12.36±0.31 µg/ml) cell lines. The IC of frullanolide was high in the human normal epithelial breast cell line (MCF-12A) and mouse fibroblast cell line (L-929). Density plot diagrams revealed that frullanolide induced apoptosis in MCF-7, MDA-MB-468 and MDA-MB-231 cells. Notably, a plausible anticancer mechanism was elucidated via cellular apoptosis by p53-independence in the treated MCF-7 cell line and p53-dependence in the treated MDA-MB-468 and MDA-MB-231 cell lines. In conclusion, the present study demonstrated that frullanolide may exert anticancer activity on breast cancer cell lines by inducing apoptosis. Frullanolide offers a possible novel approach to breast cancer therapy.
乳腺癌是全球女性死亡的主要原因。尽管有几种现代乳腺癌治疗方法，但大多数治疗方法的复发率都很高；因此，寻找有效的抗癌药物的工作仍在继续。本研究旨在研究从植物中分离纯化得到的化合物弗罗内酯对选定的人乳腺癌细胞系（MCF-7、MDA-MB-468和MDA-MB-231）的抗乳腺癌潜力。采用MTT法评估弗罗内酯在1.25、2.5、5.0、10.0和20.0μg/ml浓度下对乳腺癌细胞系的细胞毒性活性。此外，通过流式细胞术和蛋白质印迹分析研究了弗罗内酯在不同浓度[0.5×、1×和2×半数最大抑制浓度（IC）]下的凋亡诱导能力。弗罗内酯对MDA-MB-468细胞系表现出较强的抗乳腺癌活性（IC，8.04±2.69μg/ml），对MCF-7细胞系（IC，10.74±0.86μg/ml）和MDA-MB-231细胞系（IC，12.36±0.31μg/ml）表现出较弱的细胞毒性。弗罗内酯在人正常乳腺上皮细胞系（MCF-12A）和小鼠成纤维细胞系（L-929）中的IC较高。密度分布图显示弗罗内酯可诱导MCF-7、MDA-MB-468和MDA-MB-231细胞凋亡。值得注意的是，通过对处理后的MCF-7细胞系中p53非依赖性和处理后的MDA-MB-468和MDA-MB-231细胞系中p53依赖性的细胞凋亡，阐明了一种合理的抗癌机制。总之，本研究表明弗罗内酯可能通过诱导凋亡对乳腺癌细胞系发挥抗癌活性。弗罗内酯为乳腺癌治疗提供了一种可能的新方法。
