EFFECTS OF CARDIAC GLYCOSIDES FROM DIGITALIS AND CHAN SU ON THE PROLIFERATION OF HUMAN PROSTATE CANCER CELL LINES
| Autor: | Jiun-Yih Yeh, 葉濬毅 |
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| Rok vydání: | 2002 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 90 Some studies have revealed that digitalis and Chan Su extracts possessed cytostatic or oncolytic effects in various tumor cells. This study was performed to study the effects of three kinds of digitalis including digoxin, digitoxin and ouabain, and two kinds of Chan Su extracts including bufalin and cinobufagin on the proliferation and possible mechanism in androgen-dependent prostate cancer cell lines LNCaP, or androgen-independent prostate cancer cell lines DU145 and PC3. MTT colorimetric assay was performed to detect the proliferation of prostate cancer cell lines after treatment of digoxin, digitoxin, ouabain, bufalin or cinobufagin. The cytotoxicity of five drugs to three cell lines was evaluated by lactate dehydrogenase activity detection. Intracellular calcium concentration was detected by fura2 and a two-wavelength spectrophotometer. The percentage of apoptotic cells treated with drugs was evaluated by the method of TdT-mediated fluorescein-dUTP Nick-End Labeling combined with flow cytometry. The activities of three caspases including caspase-3, 8 and 9 were measured by a colorimetric method. Results indicated that cell proliferation rate was significantly inhibited by digitalis or Chan Su extracts and the intracellular calcium and percentage of apoptotic cells were increased dose dependently. The drugs also increased caspases activities. In conclusions, digitalis and Chan Su extract can directly inhibit the proliferation of both the androgen-dependent prostate cancer cell line LNCaP and the androgen-independent prostate cancer cell lines DU145 and PC3. This effect is possibly partially through an elevation of intracellular Ca2+ and by the appearance of apoptosis induced by the elevated activities of various types of caspases. The three prostate cancer cell lines showed different degree of sensitivity to cardiac glycosides treatment. Since cardiac glycosides are drugs of narrow therapeutic safety, more detailed in vitro intoxication trials on various normal human cells are needed before wide-range in vivo studies are started. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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