RESUMO
OBJECTIVE: Human seminal plasma has diverse biological activities including cytotoxic effect. It contains high concentrations of zinc and citric acid. Zinc inhibits several carcinoma cell growths through induction of cell cycle arrest and apoptosis. We tried to investigate the effects of zinc-citrate compound (CIZAR(R)) on normal human ovarian epithelial (NOSE) cells and human epithelial ovarian cancer cells, OVCAR-3. METHODS: To investigate the potential effect of CIZAR(R) on cell growth and survival, cells were treated with different dose and exposed to different time. Mitochondrial(m)-aconitase activity was determined in cell extracts using aconitase assay. The flow cytometric assay, DNA laddering, telomerase activity and morphological analysis were done to investigate apoptosis of OVCAR-3 cells. Molecular mechanism of apoptosis was investigated by p53, Bcl-XL, Bcl-2, Bax protein, and caspase activity. RESULTS: Treatment of OVCAR-3 cells with CIZAR(R) resulted in a time- and dose-dependent decrease in cell number in comparison with NOSE cells. M-aconitase activity was significantly decreased in OVCAR-3 cells but relatively constant in NOSE cells. The flow cytometric assay, DNA laddering and morphological analysis indicated apoptosis of OVCAR-3 cells. CIZAR(R) did not affect p53 but increased the expression of p21waf1 upon the indicated times and induced reduction of telomerase activity. CIZAR(R) reduced expression of Bcl-2 and Bcl-xL proteins but induced expression of Bax protein. CIZAR(R) induced apoptosis of OVCAR-3 cells by activation of caspase-3 pathway. CONCLUSION: These results show that CIZAR(R) prevent the proliferation of OVCAR-3 cells by inactivation of m-aconitase activity and induce apoptosis by induction of apoptotic genes and repression of antiapoptotic genes without adverse effect on normal ovarian epithelial cells. These results will offer new window in prevention and treatment of epithelial ovarian cancer.
Assuntos
Humanos , Aconitato Hidratase , Apoptose , Proteína X Associada a bcl-2 , Proteína bcl-X , Caspase 3 , Contagem de Células , Pontos de Checagem do Ciclo Celular , Extratos Celulares , Ácido Cítrico , DNA , Células Epiteliais , Nariz , Neoplasias Ovarianas , Repressão Psicológica , Sêmen , Telomerase , ZincoRESUMO
Cervical carcinoma is the second leading cause of death from cancer in women worldwide. It is well known that human papillomaviruses (HPVs) is the etiologic agent of cervical neoplasia and cervical cancer. Zinc has been shown to inhibit the growth of malignant cell lines by inducing apoptosis and cell cycle arrest. Recently it was reported that zinc-citrate compound (CIZAR(R)) has a cytotoxic effect on choriocarcinoma cell line and ovarian adenocarcinoma cell line and suppresses its proliferation inducing apoptosis. CIZAR(R) prevents the proliferation by inactivation of m-aconitase activity and induces apoptosis by increasing Bax expression and reducing Bcl-2 expression and inactivation of telomerase. We report one patient of cervical adenocarcinoma with HPV infection, who desires to continue pregnancy, treated by daily topical application of SeLava(R) which contains zinc-citrate compound (CIZAR(R)). We followed up the cytologic, pathologic and coloposcopic changes of healing process.