title: Glycine soya diet synergistically enhances the suppressive effect of tamoxifen and inhibits tamoxifen-promoted hepatocarcinogenesis in 7,12-dimethylbenz[α]anthracene-induced rat mammary tumor model.
abstract: There is increasing interest in phytoestrogens as potential alternatives to synthetic selective estrogen receptor modulators (SERMs) in the prevention and therapy of breast cancer. The present study is aimed at determining whether dietary glycine soya (Glycine max seeds; GS), which is rich in phytoestrogens, can enhance the anti breast cancer efficacy of the SERM tamoxifen (TAM) and the effect of TAM and GS, either alone or in combination, on DMBA-initiated hepatocarcinogenesis in rat. For determination of enhancing effect, rats bearing palpable 7, 12-dimethylbenz[α] anthracene (DMBA)-induced mammary tumors were treated with TAM (10 mg kg(-1)/day) while being fed AIN-93G diet with or without added GS (3×10(4) mg kg(-1)), and the tumor growth was monitored up to 5 weeks of treatment. For determining the effect on hepatocarcinogenesis, DMBA-initiated rats were exposed to TAM and dietary GS as above for 6 weeks during promotion stage in a medium-term bioassay, and the development of placental form of glutathione-S-transferase (GST-P)-expressing preneoplastic liver lesions was quantified. Exposure to both TAM and dietary GS enhanced the anti tumor efficacy of TAM via a combination of tumor cell apoptosis (determined by TUNEL) and inhibition of tumor cell proliferation (determined by PCNA immunostaining) and suppressed the growth of GST-P-positive liver lesions. The findings show that dietary GS enhances the therapeutic efficacy of TAM against mammary tumors and minimizes TAM's hepatocarcinogenesis promotion potential.
authors.affiliation: Division of Toxicology, Central Drug Research Institute, Council of Scientific and Industrial Research (CSIR), Lucknow, India. rajeevcdri@gmail.com
authors.forename: Rajeev
authors.initials: R
authors.lastname: Mishra
authors.forename: Smrati
authors.initials: S
authors.lastname: Bhadauria
authors.forename: P K
authors.initials: PK
authors.lastname: Murthy
authors.forename: P S R
authors.initials: PS
authors.lastname: Murthy
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D004357:Drug Synergism; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D008325:Mammary Neoplasms, Experimental; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013025:Glycine max; D013629:Tamoxifen / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat