Chemoprevention of mammary tumorigenesis and chemomodulation of the antioxidative enzymes and peroxidative damage in prepubertal Sprague Dawley rats by Biochanin A.
Although chemopreventive action of Biochanin A against various cancers including that of prostate, breast, colon, and fore-stomach has been reported earlier, none of the studies was made in prepubertal subjects. The present study appears to be the first one on prepubertal rats that indicates the efficacy of the test compound in the prevention of tumorigenesis. The antioxidative status and xenobiotic metabolism were also evaluated to understand the mechanism of Biochanin A induced prevention of cancer. For the tumorigenesis study 500 microg/g bwt of Biochanin A or vehicle dimethyl sulfoxide (DMSO) s.c, was injected at 16th, 18th, and 20th days post-partum followed by the administration of dimethylbenz[a]nthracene (DMBA) (80 microg/g bwt) at 50th day. In another set of experiments, to study the involvement of peroxidative process in the mechanism of action of test compound, different antioxidant parameters were studied following the administration of two different doses of Biochanin A (0.5 and 50 mg/kg bwt, through oral gavage for 10 days) in the prepubertal rats from day 16 post-partum. Results showed a significant reduction in the mammary tumors (more than 40%) in Biochanin A treated animals, as compared to animals treated with DMBA only. Spectrophotometric enzyme estimations revealed that the specific activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione transferase (GST), DT-diaphorase (DTD), and reduced glutathione (GSH) levels were increased, whereas specific activities of lactate dehydrogenase (LDH) and lipid peroxidation (LPO) were decreased significantly, both in liver as well as in mammary gland, in animals treated with Biochanin A prepubertally. These results reveal the possible involvement of the antioxidative and metabolic enzymes in the suppression of cancer burden and incidence in a prepubertal rat model suggesting that the intake of this phytoestrogen at an early stage may help in lowering the risk of mammary tumor.
Mishra
Prachi
P
School of Life Sciences, Jawaharlal Nehru University (JNU), New Mehrauli Road, New Delhi 110067, India. prachim_2001@yahoo.com
Kale
R K
RK
Kar
Anand
A
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology; D015674:Mammary Neoplasms, Animal / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D019833:Genistein; D007770:L-Lactate Dehydrogenase; C004541:biochanin A