title: Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7, 12-dimethylbenz(a)anthracene induced mammary carcinoma in experimental rats.
abstract: Globally, breast cancer is the second most prevalent cancer among women and its incidence is amplifying alarmingly. Since genetics is believed to account for only 10% of the reported cases, the environmental factors including diet are thought to play a significant role in predisposing breast cancer. Many bioactive compounds of plant origin have been reported for their anticancer potential. Tangeretin, a pentamethoxy flavone, is a naturally occurring phytoconstituent found to be present in significant amounts in the peel of citrus fruits. Tangeretin possess a wide array of pharmacological activities such as cytostatic, anti-proliferative and antioxidant properties. In the absence of systemic studies in the literature, the present study was aimed to evaluate the chemotherapeutic potential of tangeretin in 7, 12-dimethyl benz(a)anthracene (DMBA) induced mammary carcinoma in rats. Oral treatment of tangeretin (50 mg/kg BW) to breast tumor bearing rats daily for four weeks was found to be effective against DMBA induced mammary gland carcinogenesis in female Wistar rats. The increased activities of AST, ALT, ALP, ACP, 5'-ND, γ-GT and LDH in serum of control and experimental breast cancer rats were significantly (p < 0.05) decreased to near normal levels. Further, the levels of lipid peroxide (TBARS), enzymatic antioxidants such as SOD, CAT, GPx and non-enzymatic antioxidants such as GSH, Vitamin C, Vitamin E and Phase I (cytochrome P450, cytochrome b5, EROD, MROD and PROD) and Phase II detoxification (glutathione S-transferase (GST), quinone reductase (QR)) were decreased significantly by administration of tangeretin. Immunohistochemical and western blotting studies for estrogen receptor, progesterone receptor and HER2/neu status exemplified the chemotherapeutic effect of tangeretin. Further, the histological and ultrastructural analysis of breast tissues evidenced the anti-tumorigenic nature of tangeretin. Thus, the results of the present study clearly indicate that tangeretin significantly suppresses DMBA induced breast cancer in rats.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
authors.forename: A
authors.initials: A
authors.lastname: Lakshmi
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India. Electronic address: subbus2020@yahoo.co.in.
authors.forename: S
authors.initials: S
authors.lastname: Subramanian
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000097:blood; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D047309:Flavones / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D050216:Metabolic Detoxication, Phase I; D018396:Mucin-1 / Q000097:blood; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D000972:Antineoplastic Agents, Phytogenic; D002272:Carcinoembryonic Antigen; D047309:Flavones; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D017392:Thiobarbituric Acid Reactive Substances; D000509:alpha-Fetoproteins; C059006:tangeretin
keywords: Antioxidant; Breast cancer; Chemotherapeutic agent; DMBA; Oxidative stress; Tangeretin