Ursolic acid induced apoptosis in ovarian carcinoma SKOV3 cells

Abstract

Objective To study the effect of ursolic acid(UA) on apoptosis of the ovarian cancer cell line SKOV3 and its action mechanisms. Methods The SKOV3 cells were treated with UA at different concentration. The proliferation inhibition was examined by MTT assay. Morphological examination and flow cytometry were used to detect apoptosis. RT-PCR and immunocytochemical method were used to detect the expression of wild type p53,an apoptosis related genes. The semi-quantification of protein expression was analyzed by pathological image-analysis. Results UA inhibited the proliferation of SKOV3 cells strongly. Apoptosis of SKOV3 cells were induced by UA treatment. The morphology of SKOV3 showed changes such as chromatin aggregation, nuclear and cytoplasmic condensation and apoptotie bodies appearance. UA caused significant G0/G1 arrest with a concomitant decrease of cell population in S and G2/M phases. Apoptotic cells were found by flow cytometry. The maximal early apoptotic rate was (28.7±2.4)% when exposed to 40 μmol/L for 48 h. The expression of p53 gene and protein was enhanced. All these effects were in a dose and time-dependent manner Conclusion UA induced apoptotic processes in the ovarian cancer SKOV3 cell line were the mechanism involving p53 pathway. Key words: Ursolic acid; Ovarian neoplasms; Cell line, tumor, Apoptosis; Genes, p53