Cui Hongxia, Yuan Jiaxin, Du Xiaohui, Wang Ming, Yue Liling, Liu Jicheng
Department of Clinical Pharmacology, Qiqihar Medical College, Qiqihar, Heilongjiang, P.R. China.
Heilongjiang University of Chinese Medicine, Harbin 150040, P.R. China.
Oncol Rep. 2015 Mar;33(3):1284-90. doi: 10.3892/or.2014.3682. Epub 2014 Dec 18.
Euphorbia fischeriana Steud is a traditional Chinese Medicine that is known to possess a variety of anticarcinogenic properties. However, the bioactive constituents in Euphorbia fischeriana Steud and molecular mechanisms underlying this action in cancer treatment remain poorly understood. The present study investigated the chemotherapy activity and molecular targets of Ethyl gallate, which is identified as the major constituent extracted from the roots of Euphorbia fischeriana Steud in breast cancer cell lines in vitro. The results showed Ethyl gallate obviously decreased cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner. Highly invasive MDA-MB-231 cells were found to be highly sensitive to treatment. Furthermore, significantly decreased metastatic potential of highly metastatic MDA-MB‑231 cells by Ethyl gallate was identified via the inhibition of cell motility using invasion and migration through a polyethylene terephthalate membrane. Ethyl gallate treatment decreased the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 by the downregulation of mRNA levels using RT-PCR, enzymes that are critical to tumor invasion. Treatment with Ethyl gallate decreased phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor-κB (NF-κB) activation in MDA-MB-231 cells. These results indicate that Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K/Akt pathway, which may contribute to inhibiting their downstream targets such as NF-κB p-65, Bcl-2/Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells. Thus, the present study shed new light on Ethyl gallate, an important bioactive constituent of Euphorbia fischeriana Steud, in human breast cancer treatment. The findings may provide basal theories for wide therapeutic application in human breast cancer.
狼毒大戟是一种传统中药，已知具有多种抗癌特性。然而，狼毒大戟中的生物活性成分及其在癌症治疗中的作用分子机制仍知之甚少。本研究调查了没食子酸乙酯的化疗活性和分子靶点，没食子酸乙酯是从狼毒大戟根中提取的主要成分，在体外乳腺癌细胞系中进行研究。结果表明，没食子酸乙酯以剂量和时间依赖性方式显著降低MDA-MB-231和MCF-7细胞的增殖。发现高侵袭性的MDA-MB-231细胞对治疗高度敏感。此外，通过使用聚对苯二甲酸乙二酯膜进行侵袭和迁移实验抑制细胞运动，确定没食子酸乙酯显著降低高转移性MDA-MB-231细胞的转移潜能。没食子酸乙酯处理通过逆转录聚合酶链反应下调基质金属蛋白酶-2（MMP-2）和MMP-9的mRNA水平，从而降低其活性，这两种酶对肿瘤侵袭至关重要。没食子酸乙酯处理降低了MDA-MB-231细胞中磷脂酰肌醇3-激酶（PI3K）/Akt和核因子-κB（NF-κB）的激活。这些结果表明，没食子酸乙酯通过调节PI3K/Akt途径抑制人乳腺癌细胞的增殖和侵袭，这可能有助于抑制其下游靶点，如乳腺癌细胞中的NF-κB p-65、Bcl-2/Bax以及MMP-2和MMP-9的mRNA水平。因此，本研究为狼毒大戟的重要生物活性成分没食子酸乙酯在人类乳腺癌治疗中的应用提供了新的线索。这些发现可能为其在人类乳腺癌广泛治疗应用中提供基础理论。
