Cytotoxic and apoptotic effects of cyproterone acetate against cancer cells and normal cells

Abstract

Back ground: Cyproterone acetate (CPA) is a steroidal anti-androgen inhibits the testosterone  and  DHT action it is used as a medicine for prostate cancer by association with the androgen receptors located on the surface of prostate cells, thus preventing the association of testosterone with receptors.

Objective: Investigation of the anticancer activities of Cyproterone acetate   against cancer cell lines testicular (Tera-1), macrophage (RAW 264.7)  in comparison to non- tumorigenic fetal hepatic cell line (WRL-68).

Material and method: The cytotoxic effect of CPA was investigated according to selected parameters including: MTT assay as assay of cell function to determined cell viability, high content screening (HCS) technique for the apoptosis of cell. Only the most cytotoxic concentration of CPA and the most sensitive cells  as assayed by MTT was selected to complete the other test: (HCS). (MTT) assay was carried out at the Centre of Biotechnology Research’s, Al- NahrainUniversityBaghdad,Iraq . The HCS assay was performed at the Centre for Natural Product Research and Drug Discovery, Department of Pharmacology,Faculty of Medicine, University of Malaya, KualaLumpur, Malaysia

Results: The most significant cytotoxic effect of Cyproterone acetate towards 2 cancer cell lines was obtained when its concentration was 1.25mg/mL. The Tera-1 Cells were more sensitive to Cyproterone acetate compared with RAW264.7  and  WRL-68. cells. There was a significant decrease  in valid cell count, nuclear intensity and mitochondrial membrane potential (MMP) when CPA (400 μg/mL)was used compared with doxorubicin (20 μg/mL) as a standard. Also, there was a significant increase in membrane permeability and cytochrome C releasing when CPA (400μg/ml) was used compared with positive control.

Conclusion: CPA showed cytotoxic effects against the Tera-1 and RAW264.7  cancer cell lines while the WRL-68. Cells was not affected as determined in-vitro by the MTT assay. The HCStechnique also showed toxic effect towards Tera-1.