Studies on the Anticancer Activity of Ganoderic Acid T in Lung Cancer Cells
| Autor: | Hsiao-Hsuan Lai, 賴曉萱 |
|---|---|
| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 Lung cancer is one of the most common malignant diseases with a dismal prognosis; the high mortality rate has made it one of the leading causes of cancer-related death over the past years. Despite of advances in early detection and cancer therapy, most patients with lung cancer present with advanced disease and their long-term prognosis remains poor. Therefore, providing an effective treatment for lung cancer is important. Lingzhi has long been reputed as anticancer medicinal mushroom in folk medicine. The bioactive component triterpenoids have been known as anticancer ingredients of the medicinal mushroom. As adenocarcinoma is the most prevalent subtype of lung cancer, we are interested in investigating the anti-cancer efficacy of a ganoderma triterpenoid, ganoderic acid T (GAT), in lung adenocarcinoma cells. Our data revealed that GAT displayed growth inhibitory and cytotoxicity effects on various lung adenocarcinoma cell lines whereas it exerted no effect on the survival of normal human peripheral blood mononuclear cells. The mechanism of GAT-induced cytotoxicity was studied further and GAT was found to induce irreversible autophagic response thus resulted in autophagic cell death in highly proliferative A549 cells. Besides, as lung cancer is considered to be highly metastatic and a great majority of patients are found with distant metastases, we also accessed the anti-metastatic potential of GAT. Epithelial-mesenchymal transition (EMT) is a biological process which allows stationary epithelial cells to become motile. By using a TGF-β-induced-EMT cell model, GAT was found to act as a protective role in TGF-β-induced-EMT through blocking ROS generation, pERK activation and the EMT-activator Slug expression thus prevent further cell morphological change, transcriptional regulation (including E-cadherin loss as well as N-cadherin and CXCR4 up regulation) and further cell migration. Finally, the anti-cancer efficacy of GAT in vivo was confirmed in SCID mouse xenograft model. The results of animal experiments indicated that intra-tumor GAT injection can restrain the growth of A549 tumors subcutaneously implanted in the mice and prevent further hepatic metastasis. Besides, oral treatment of GAT can successfully restrain the growth of A549 tumors and exerts no toxicity to SCID mice. Taken together, the anticancer activity of triterpenoids from Lingzhi is confirmed in this study. Thus, GAT is a potential anti-cancer agent or therapeutic drug adjuvant for cancer treatment. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|