Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells

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Abstract
Background Cardiac glycosides may induce oncolytic effects in cancers. This study was to evaluate bufalin and cinobufagin effects on the proliferation of prostate cancer cell lines named LNCaP, DU145, and PC3. Methods Cell proliferation was measured by MTT assay. The cytotoxic effects were determined by lactate dehydrogenase measurements. The intracellular calcium concentration ([Ca2+]i) was measured by a dual-wavelength spectrometer system. TUNEL assay and flow cytometry were performed to measure percentage of apoptotic cells. A colorimetric assay was to measure caspases activities. Results Bufalin and cinobufagin inhibited proliferation of cancer cells at doses of 0.1, 1, or 10 μM after 2–4 days of culture. Cytotoxicity of bufalin and cinobufagin on the DU145 and LNCaP cells was dose-dependent. Bufalin or cinobufagin increased [Ca2+]i and apoptosis in cancer cells after a 24-hr culture as well as caspase 3 activities in DU145 and PC3 cells and caspase 9 activities in LNCaP cells. Conclusions Bufalin and cinobufagin may inhibit the proliferation of prostate cancer cell lines associated with sustained elevation of the [Ca2+]i and that of apoptosis. Prostate 54: 112–124, 2003.