ABSTRACT
Phytoestrogen genistein can exhibit cytoprotective and antioxidant properties, providing chemopreventive action, and produce cytotoxic effects on some tu- mors. In this work, the cytotoxic, cytoprotective, and antioxidant properties of genistein have been studied on model tumor cells (human cervical cancer HeLa cells) and normal cells (rat dermal fibroblasts, RDF). For assessing the cytotoxic effect of genistein (spectrophotometric MTT assay), the reference drug was cis-diaminodichloroplatinum (cisplatin); for evaluating antioxidant action, beta-estradiol was the reference drug. It is established that genistein produces a cyto- toxic effect only at high concentrations, IC50 = 20 mM and 14 mM for RDF and HeLa cells, respectively, which is 30 and 10 times higher than IC50 for cisplatin on these cells. Genistein like estradiol, but unlike cisplatin, had no effect on the mitochondrial pore induction from rat liver mitochondria. Thus, genistein at physiological concentrations (up to 200 n) acts as a cytoprotective agent. High antioxidant activity of genistein also suggests the possibility of its use as a chemopreventive drug.
Subject(s)
Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Fibroblasts/drug effects , Genistein/pharmacology , Phytoestrogens/pharmacology , Animals , Cell Survival/drug effects , Free Radicals/chemistry , HeLa Cells , Humans , Inhibitory Concentration 50 , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Permeability Transition Pore , Rats, WistarABSTRACT
In this paper we study the effect of synthetic isoflavonoid genistein against cancer HeLa cells, which contain estrogen receptors alpha but not beta, with the aim to determine the cytotoxic or cytoprotective effect of genistein. It is shown that the half maximal inhibitory concentration (IC50) value of genistein (0.2 mM) for the growth inhibition of HeLa cells is at least ten times higher than that one of tamoxifen and cisplatin--drugs, used in cervical cancer treatment. In micromolar concentrations (0.1-10 µM) genistein decreased the cytotoxic effects of cisplatin and tamoxifen. The decreased Bax mRNA expression and increased Bcl-2 mRNA expression after incubation .of the cells with genistein also demonstrate the cytoprotective, anti-apoptotic effect of genistein. Genistein, even in high concentrations, had no effect on membrane potential and calcium capacity of isolated mitochondria, without activating the opening of Ca(2+)-induced mitochondrial pore. Thus, these data demonstrate a cytoprotective effect of isoflavonoid genistein against this type of cancer cells.
Subject(s)
Apoptosis/drug effects , Genistein/administration & dosage , Neoplasm Proteins/biosynthesis , Phytoestrogens/administration & dosage , Cell Proliferation/drug effects , Estrogen Receptor alpha/biosynthesis , Gene Expression Regulation, Neoplastic/drug effects , HeLa Cells , Humans , Membrane Potentials/drug effects , Proto-Oncogene Proteins c-bcl-2/biosynthesis , RNA, Messenger/biosynthesisABSTRACT
Estrone, estriol, and estradiol valerate exhibited antiarrhythmic activity in rats with aconitine-induced arrhythmia. Estrone was most effective in this respect.
