Effects of Ginkgo biloba on chemically-induced mammary tumors in rats receiving tamoxifen

Monday, 20/05/2013  |   estrogen positive tumours, Others  |  no comments

Source:Dias MC, et al. BMC Complementary and Alternative Medicine 2013, 13:93 doi:10.1186/1472-6882-13-93 Ginkgo The majority of breast cancers are estrogen-dependent disease with increasing morbidity and mortality rates in most western societies over the last few decades [1-3]. The most common therapeutic strategies for breast cancer, including excision surgery (mastectomy),radiotherapy, chemotherapy, monoclonal antibodies and endocrine therapies, impact on women’s quality of life [4]. As an endocrine adjuvant therapy, anti-estrogenic drugs target the estrogen receptor (ER)-dependent intracellular response by directly binding to andinhibiting ERs (Selective Estrogen Receptor Modulators, SERMs) or by down-regulating the synthesis of endogenous estrogens (Aromatase Inhibitors, AIs) [5,6]. The SERMs, which include TAM and Raloxifen, have been established

as gold standard first-line therapies forestrogen-dependent breast cancers [7]. TAM has been found to reduce the incidence of breast cancer in high-risk pre- and post-menopausal women and to enhance disease-free survival and reduce disease recurrence [8]. However, an extensive evaluation of TAM use has revealed some side effects such as increased risk for endometrial cancer, deep-vein thrombosis and pulmonary embolism [9-11]. These important side effects have resulted in the use of alternative treatments such as complementary and alternative medicine (CAM). Popular interest in CAM has grown rapidly over the past decade in the western world [12]. Commercial advertisements, many of which promise cures, have stimulated the consumption of CAM treatments including herbal, vitamin and nutritional supplements. The use of CAM is more common among cancer patients than among the general population [12]. Recent reports estimate that 7-64% of chemotherapy patients in 26 cohort studies worldwide have used herbal supplements [13,14], and up to 72% of these patients did not inform their physician about their concomitant CAM usage [15]. Although the use of herbal or ‘natural’ drugs is rapidly growing, most of these promising therapies remain poorly understood, and limited scientific evidence regarding their efficacy and safety is available [16]. Thus, preclinical and clinical studies are necessary to evaluate the safety and efficacy of each CAM alone and/or in combination with prescription drug therapies. Ginkgo biloba extract (GbE) is a well-established medicinal herb extensively used as a CAM in diseases including breast cancer [17]. GbE is a complex mixture of over 300 compounds primarily composed of flavonoid glycosides and terpenoids such as ginkgolides andbilobalides [17,18]. GbE has been used for the prevention and treatment of bra in disorders, systemic circulatory disorders, memory loss and Alzheimer’s disease [17,19,20]. In fact, many molecules within GbE have been shown to exhibit pharmacological properties such as cell cycle regulatory, antioxidant, anti-proliferative, anti-angioge nic and anti-estrogenic activities [21]. As GbE is used extensively as a CAM [17] and is used by breast cancer patients undergoing treatment with TAM [22], the present study was designed to investigate the effects of Ginkgo biloba extract in a chemically induced mammary tumor model in female SD rats treated with Tamoxifen. Ginkgo biloba extract (GbE) is used extensively by breast cancer patients undergoing treatment with Tamoxifen (TAM). Thus, the present study investigated the effects of GbE in female Sprague–Dawley (SD) rats bearing chemically-induced mammary tumors and receiving TAM. Overall, the tumor volume and the PCNA LI% within live tumor areas were reduced by 83% and 99%, respectively, in all TAM-treated groups when compared to the untreated control group. GbE treatment (100 mg/kg) reduced the proportions of live (24.8%) and necrotic areas (2.9%) (p = 0.046 and p = 0.038, respectively) and significantly increased the proportion of degenerative areas (72.9%) (p = 0.004) in mammary tumors when compared to the group treated only with TAM. The expression of ER-?, p63 and cleaved caspase-3 in live tumor tissues was not modified by GbE treatment.ConclusionsCo-treatment with 100 mg/kg GbE presented a slightly beneficial effect on the therapeutic efficacy of TAM in female SD rats bearing mammary tumors. References1. Cuzik J. Breast cancer prevention in the developing world. Breast Cancer Res 2010, 12 (Suppl 4):S9.2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistic. CA Cancer J Clin 2011, 61:69–90.3. Bouchardy C, Fioretta G, Verkooijen HM, Vlastos G, Schaefer P, Delaloye JF, Neyroud-caspar I, Balmer-Majno S, Wespi Y, Forni M, et al. Recent increase of breast cancer incidence among women under the age of forty. Br J Cancer 2007,96:1743–1746.4. Dierssen JW. High-resolution analysis of HLA class I alterations in colorectal cancer. BMC Cancer 2006, 6:233.5. Park WC, Jordan VC. Selective estrogen receptor modulators (SERMS) and their roles in breast cancer prevention. Trends Mol Med 2002, 8:82–88.6. Bush NJ. Advances in hormonal therapy for breast cancer. Semin Oncol Nurs 2007,23:46–54.7. Silverman SL. New selective estrogen receptor modulators (SERMs) in development. Curr Osteoporos Rep 2010, 8:151–153.8. Jordan VC. Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer. British J Pharm 2006, 147:269–276.9. Brown K. Is tamoxifen a genotoxic carcinogen in women? Mutagenesis 2009, 24:391–404.10. White INH. The tamoxifen dilemma. 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