Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
Biochimie. 2014 Apr;99:96-109. doi: 10.1016/j.biochi.2013.11.017. Epub 2013 Dec 1.
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.
全球范围内，乳腺癌是女性中第二常见的癌症，其发病率令人震惊地不断增加。由于遗传因素据信仅占报告病例的 10%，因此环境因素包括饮食被认为在导致乳腺癌方面起着重要作用。许多植物来源的生物活性化合物已被报道具有抗癌潜力。桔皮素是一种五甲氧基黄酮，是一种天然存在的植物成分，在柑橘类水果的果皮中含量很高。桔皮素有广泛的药理活性，如细胞抑制、抗增殖和抗氧化作用。由于文献中缺乏系统研究，本研究旨在评估桔皮素在 7,12-二甲基苯并（a）蒽（DMBA）诱导的大鼠乳腺肿瘤中的化疗潜力。桔皮素（50mg/kgBW）对荷瘤大鼠的口服治疗，每周 4 次，共 4 周，对雌性 Wistar 大鼠的 DMBA 诱导乳腺腺癌细胞发生有效。对照组和实验性乳腺癌大鼠血清中 AST、ALT、ALP、ACP、5'-ND、γ-GT 和 LDH 的活性显著升高（p<0.05），接近正常水平。此外，脂质过氧化物（TBARS）、SOD、CAT、GPx 等酶抗氧化剂和 GSH、维生素 C、维生素 E 等非酶抗氧化剂以及细胞色素 P450、细胞色素 b5、EROD、MROD 和 PROD）和 II 相解毒（谷胱甘肽 S-转移酶（GST）、醌还原酶（QR））水平显著降低。桔皮素给药后，雌激素受体、孕激素受体和 HER2/neu 状态的免疫组织化学和 Western blot 研究说明了桔皮素的化疗作用。此外，乳腺组织的组织学和超微结构分析证明了桔皮素的抗肿瘤特性。因此，本研究的结果清楚地表明，桔皮素可显著抑制 DMBA 诱导的大鼠乳腺癌。
