- 作者: Dong-Ming Huang a, Jih-Hwa Guh b, Yao-Ting Huang a, Shih-Chieh Chueh c, Hui-Po Wang d, Che-Ming Teng a
- 作者服務機構: a Pharmacological Institute, b school of Pharmacy, College of Medicine, National Taiwan University, c Department of Urology, National Taiwan University Hospital, Taipei, d Graduate Institute of Natural Products, College of Medicine, Chang-Gung University, Tao-Yuan, Taiwan , ROC
- 中文摘要: --
- 英文摘要: Using in situ immunofluorescent detection of mitoticspindles, our data showed that cardiac glycosides dimin-ished paclitaxel-induced accumulation of microtubulespindles; however, in a non-cell assay system, cardiacglycosides had little influence on colchicine- and pacli-taxel-induced microtubule dynamics. Using an isotope-labeled assay method, we found that ouabain modestlybut significantly inhibited the transport of [ C]paclitaxelfrom the cytosol into the nucleus. It is suggested that car-diac glycosides inhibit the G2/M arrest induced by tubu-lin-binding anticancer drugs via an indirect blockade onmicrotubule function. The decline in transport of thesedrugs into the nucleus may partly explain the action ofcardiac glycosides.Due to high prevalence and mortality and the lack ofeffective therapies, prostate cancer is one of the mostcrucial health problems in men. Drug resistance aggra-vates the situation, not only in human prostate cancerbut also in other cancers. In this study, we report for thefirst time that cardiac glycosides (e.g. ouabain and digi-toxin) induced resistance of human prostate cancer cells(PC-3) in vitro to tubulin-binding anticancer drugs, suchas paclitaxel, colchicine, vincristine and vinblastine. Car-diac glycosides exhibited amazing ability to reverse theG2/M arrest of the cell cycle and cell apoptosis inducedby tubulin-binding agents. However, neither ionomycin(a Ca ionophore) nor veratridin (a Na ionophore)mimicked the preventive action of cardiac glycosides,indicating that elevation of the intracellular Ca concen-tration and Na+ accumulation were not involved in thecardiac glycoside action. Furthermore, cardiac glyco-sides showed little influence on the effects induced byactinomycin D, anisomycin and doxorubicin, suggestingselectivity for microtubule-targeted anticancer drugs.
- 中文關鍵字: --
- 英文關鍵字: Cardiacg, ycoside, Tubulin, Paclitaxel, Prostate cancer, Resistance