Anti-tumor effect and mechanism of cytopiloyne aglycone in TS/A mammary gland tumor-bearing mice
| Autor: | Kai-Wei Chen, 陳凱偉 |
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| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 Breast cancer is a leading cause of death in women worldwide. For the past 25 years, 70 % of anticancer drugs have been developed from natural products or their derivatives. However, a major obstacle to a successful cancer therapy is the problems of drug resistance in cancer patients. Therefore, there is a need to seek new anti-cancer drugs with different mechanisms. Bidens pilosa is commonly used as a food or folk medicines for different diseases. We and other groups have identified cytopiloyne aglycone (CPA) from B. pilosa. CPA was reported to inhibit angiogenesis in human umbilical vein endothelial cells (HUVEC). However, the anti-tumor effects and mechanisms of CPA are poorly understood. In this study, we first investigated the effect of CPA on the cell growth of TS/A, MCF-7 and MDA-MB-231 cells. We found that CPA inhibited tumor cell growth in a dose dependent manner. The IC50 value for TS/A, MCF-7 and MDA-MB-231 cells were 3.12, 3.37 and 3.56 μg/ml, respectively. Furthermore, low dose of CPA inhibited TS/A cell proliferation and the effect on anti-proliferation was persistent and irreversible. High dose of CPA have cell cytotoxity to induce apoptosis of TS/A cells, as revealed by induce the caspase 3/7 activity in flow-cytometer data. We assessed anti-tumor effect of CPA in TS/A tumor-bearing BALB/c mice. We found that CPA treatment at 0.02, 0.1, 0.5 mg/kg suppressed the growth of TS/A tumors compared with control group mice, as evidenced by tumor size and mass via 24 days treatment period. And mice did not show serious symptoms of toxicity. The immunohistochemical staining results showed that the tumors from CPA-treated mice exhibited reduced cell proliferation and increased apoptosis compared with tumor from control group mice. Finally, the survival rate of any CPA-treated groups was prolonged significantly. The MDSC of bone marrow and spleen from PTX and CPA-treated mice were reduced. In conclusion, CPA had the effect of anti-tumor in breast cancer both in-vitro and in-vivo with reduced cell proliferation and induced cell apoptosis. There studies of CPA for chemotherapy medicine against breast cancer are thus warranted. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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