蘋果多酚抑制人類乳癌細胞生長之分子機制研究

乳癌為女性常見的ㄧ種癌症並且具有非常高的復發率。類黃酮化合物具有預防或治療人類惡性腫瘤的效果，包括乳癌。蘋果多酚根據研究顯示具有抗腫瘤、 抗氧化和抗發炎等作用。因此本實驗利用蘋果多酚是否能夠影響人類乳癌細胞（MDA-MB-231）的生長，並進一步釐清可能的機轉。以不同劑量AP (0, 0.1, 0.3, 0.5, 0.7, 1, 2, 3 mg/ml) 分別處理MDA-MB-231細胞，利用MTT試驗來觀察細胞存活情形；實驗結果顯示，蘋果多酚可以有效抑制MDA-MB-231細胞的生長，同時利用流式細胞儀分析了細胞週期的變化，結果顯示在處理蘋果多酚後能夠誘導乳癌細胞使其細胞週期停滯在G2/M phase的現象，並探究其分子機轉，是透過PI3K pathway影響其生理作用，同時抑制Cyclin A及Cyclin B的濃度，增加CDKI - p21及p27濃度，並增加Chk2導致Cdc25c磷酸化，而使 Cdc2 減低進而造成細胞週期停滯在G2/M 期。

Breast cancer is the most commonly diagnosed cancer with a very high recurrence rate in women. Flavonoid phytochemicals possess the effect of prevention or therapeutic effect in human malignancies including breast cancer. Apple polyphenols (AP) were shown to possess anti-cancer, anti-oxidation, and anti-inflammation. Herein, it was aimed to examine the effect of AP in human breast cancer cell (MDA-MB-231 cells) and further to elucidate the possible mechanisms. After treating MDA-MB-231 cells with AP at various concentration (0, 0.1, 0.3, 0.5, 0.7, 1, 2, and 3 mg/ml), the cells were collected. MTT assay was conducted to detect the cell viability. The change of cell cycle was analyzed by using Flow cytometry, and the expressions of relative proteins were detected by immunoblot assay. The results showed AP reduces cell viability in a dose-dependent manner. In flow cytometric analysis, it showed that AP induced G2/M phase arrest. The mechanisms would be related to altering the expression of survival regulatory proteins, such as PI3K/Akt. we conclude that AP arrests MDA-MB 231 cells at G2/M phase through by inhibiting cyclin A level, cyclin B1 in high concentration of PA, and Cdc2 by increasing p21 and p27 levels, by increasing chk2 causing an increasing cdc25c phosphorylation / inactivation inducing a decrease in cdc2 levels.