PART 1：Studies on the Mechanism of SY-1 Induced Apoptosis and G0/G1 Cell Cycle Arrest in Human Colon Adenocarcinoma CellsPART 2：Studies on the Role of LOX(Lysyl Oxidase) in Breast Cancer

• Main Authors: Hsiao-Wei Lin, 林曉薇
• Other Authors: Yuan-Soon Ho
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/67773444942127398008

碩士 === 臺北醫學大學 === 醫學科學研究所 === 97 === PART 1：In this study, 4,7-dimethoxy-5-methyl-l,3-benzodioxole ( designated as SY-1 ) was isolated from three different sources of dried fruiting bodies of Antrodia camphorate (AC). AC is a medicinal mushroom that grows on the inner heartwood wall of the endemic species Cinnamomum kanehirai Hay (Lauraceae), and is used in Chinese medicine for its anti-tumor and immunomodulatory activities. We demonstrated that SY-1 profoundly decreased growth of human colon cancer cells (COLO 205) through G0/G1 cell cycle arrest (75-225μM) and induction of apoptosis (> 225μM). Cell cycle arrest induced by SY-1 was associated with a significant increase in protein levels of p53, p21/Cip1, and p27/Kip1, and a decrease in cyclins D1, D3, and A. In contrast, in normal human colonic epithelial cells (FHC), SY-1 treatment did not induce significant changes in G0/G1 phase cell cycle regulatory proteins. The cells were cultured in soft agar for evaluation of anchorage-independent colony formation, and the number of transformed colonies was significantly reduced in the SY-1-treated COLO 205 cells. These findings demonstrate, for the first time, that SY-1 inhibits human colon cancer cell proliferation through inhibition of cell growth and anchorage-independent colony formation in soft agar. PART 2：Lysyl oxidase (LOX) has been show previously, is an extracellular cupper enzyme that initiates the crosslinking of collagens and elastin. LOX catalyzes the oxidation of the side chain of a peptidyl lysine converting specific lysine and hydroxylysine residues of α–aminoadipic-δ-semialdehydes. Current findings have shown that LOX is required for the development of major organs, and have assigned it highly important roles in development and diseases in terms of migration, invasion, epithelial-mesenchymal transition (EMT) and even intracellular signalling. Form real time PCR data, we can see that LOX mRNA level in breast cancer tissues are higher than in normal tissues. It has been show previously, LOX protein was up-regulated in a lot of cancer tissue, included liver cancer and breast cancer. Laser capture microdissection (LCM) and IHC shows that LOX mRNA was over-expressed in breast cancer tissue. These results suggest that LOX facilitates migration and cell-matrix adhesion formation in invasive breast cancer cells through a hydrogen peroxide–mediated mechanism involving the FAK/Src signaling pathway.Treatment of the invasive breast cancer cell line, MDA-MB-231, with β-aminopropionitrile (βAPN), an irreversible inhibitor of LOX catalytic activity,lead to a significant decrease in cell motility/migration. Moreover, a decrease in activated focal adhesion kinase (FAK) and Src kinase, key proteins involved in adhesion complex turnover, was observed when invasive breast cancer cells were treated with βAPN. So, we predict that LOX may play an important role in breast cancer growth.