Proteomic characterization of LYF-17 causes apoptosis of breast cancer cells

• Main Authors: Liang-Chih Liu, 劉良智
• Other Authors: 高振益
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/7zc3ps

博士 === 國立中興大學 === 生物化學研究所 === 101 === Breast cancer is the most frequently diagnosed malignancy among women, with approximately one million new cases diagnosed worldwide annually. Overexpression of HER-2/neu has been associated with advanced disease, metastasis, and poor clinical outcome in breast cancer. Our preliminary experimental studies demonstrate that quinolone derivatives can inhibit HER2/neu-overexpressing breast cancer cell growth. Quinolone derivatives cause cycle arrest at G2/M phase in HER2/neu-overexpressing breast cancer cell lines. LYF-17 is a kind of Flavonols. Many beneficial properties have been attributed to Flavonols, including anti-carcinogenic, anti-tumor, anti-inflammation, and anti-oxidant actions. The central hypothesis of the proposed research is to identification of new proteins binding with quinolone derivatives should help in the design of new strategies to prevent cancer. Our long-range goal is to find out the possible mechanism by which quinolone derivatives can inhibit HER2/neu-overexpressing breast cancer cell growth. In our study, LYF-17 was identified as a potent and selective antitumor agent in human breast carcinoma. The effect of LYF-17 on cell cycle progression was examined by flow cytometry. The signal pathway of LYF-17 on MDA-MB-435 cells apoptosis was performed by using the 2D electrophoresis, MALDI-TOF and Western Blot. LYF-17 induced the inhibition of cells growth and apoptosis in MDA-MB-435 cells in a concentration-dependent manner. Importantly, it is less toxic to HBL-100 cell. LYF-17 caused a time-dependent accumulation of MDA-MB-435 cells in the G2-M phase. The phosphorylated Stat3 was decreased and suppressed in MDA-MB-435 cells after LYF-17 treatment in 48 hrs. The antiapoptotic proteins Bcl-2 family was down-regulated by LYF-17. These results demonstrate that LYF-17 directly blocks the Stat3 signaling pathway and suggest that the antitumor activity of LYF-17 is due to inhibition of this pathway.