The study of Mulberry anthocyanins regulating the microenvironment to inhibit gastric cancer proliferation and migration

• Main Authors: Hui-Pei Huang, 黃惠珮
• Other Authors: Chau-Jong Wang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/44273659195295658552

博士 === 中山醫學大學 === 生化暨生物科技研究所 === 101 === Plant anthocyanins are important part of diet because of their effects on modulating carcinogenesis and cardiovascular disease. Mulberry fruit has abundant anthocyanins, and our laboratory has been quantified and calculated that dried-Mulberry fruit contains 5% anthocyanins by HPLC experiment. Next, we used MTT assay, flow cytometery, TUNEL assay and Western blot to analyze the antitumor effect of Mulberry anthocyanins (MACs). MACs were isolated from the dried fruit of Mulberry and the effect of MACs was to cause the cancer cell apoptosis. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the MACs-induced AGS death. The data showed that only SB203580 had strong potential in inhibiting AGS cell apoptosis and also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas and FasL in the MACs-treated AGS cells. Therefore, we suggested that MACs mediated AGS apoptosis via the p38-FasL and tBid pathway. Evidences from clinical and experimental researches have suggested tumor-associated macrophage (TAM) functioning in tumor cell proliferation, tumor cell migration and invasion and tumor angiogenesis. Clinical studies have shown a correlation between an abundance of TAM and poor prognosis. Anthocyanins richly exist in mulberry plants and have been well characterized to have various bioactive properties. The aim of the present study is to determine the effect of the MACs the reducing macrophage contributes to gastric cancer (GC) cell migration, invasion and angiogenesis. Using cell proliferation study and flow cytometry, we find that AGS cell can induce THP1 monocyte differentiation to macrophage, which can be inhibited by treatment of MACs. The MACs inhibit proliferation, migration and metastasis of AGS cell enhanced by macrophage through regulating the secretion of MMP1, IL-6, CSF-1 and interferon-gamma by using ELISA assay. Also, after co-culture of AGS and THP1 cell, MACs can decrease the MMP2/9 levels of AGS cells. Beside, MACs can decrease the formation of tumor angiogenesis inducing by TAM in vitro and in vivo via inhibiting VEGF formation. Comprehensive, this work will provided the research model about the natural food inhibiting the tumor formation, metastasis, and angiogenesis. Besides, we can prove the mulberry anthocyanins as an efficient agent against the cancer.