title: Pomegranate extract demonstrate a selective estrogen receptor modulator profile in human tumor cell lines and in vivo models of estrogen deprivation.
abstract: Selective estrogen receptor modulators (SERMs) are estrogen receptor (ER) ligands exhibiting tissue-specific agonistic or antagonistic biocharacter and are used in the hormonal therapy for estrogen-dependent breast cancers. Pomegranate fruit has been shown to exert antiproliferative effects on human breast cancer cells in vitro. In this study, we investigated the tissue-specific estrogenic/antiestrogenic activity of methanol extract of pericarp of pomegranate (PME). PME was evaluated for antiproliferative activity at 20-320 μg/ml on human breast (MCF-7, MDA MB-231) endometrial (HEC-1A), cervical (SiHa, HeLa), ovarian (SKOV3) carcinoma and normal breast fibroblast (MCF-10A) cells. Competitive radioactive binding studies were carried out to ascertain whether PME interacts with ER. The reporter gene assay measured the estrogenic/antiestrogenic activity of PME in MCF-7 and MDA MB-231 cells transiently transfected with plasmids coding estrogen response elements with a reporter gene (pG5-ERE-luc) and wild-type ERα (hEG0-ER). PME inhibited the binding of [³H] estradiol to ER and suppressed the growth and proliferation of ER-positive breast cancer cells. PME binds ER and down-regulated the transcription of estrogen-responsive reporter gene transfected into breast cancer cells. The expressions of selected estrogen-responsive genes were down-regulated by PME. Unlike 17β-estradiol [1 mg/kg body weight (BW)] and tamoxifen (10 mg/kg BW), PME (50 and 100 mg/kg BW) did not increase the uterine weight and proliferation in ovariectomized mice and its cardioprotective effects were comparable to that of 17β-estradiol. In conclusion, our findings suggest that PME displays a SERM profile and may have the potential for prevention of estrogen-dependent breast cancers with beneficial effects in other hormone-dependent tissues.
authors.affiliation: Integrated Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O., Thiruvananthapuram, Kerala 695014, India. sreejasreeharshan@yahoo.com
authors.forename: Sreekumar
authors.initials: S
authors.lastname: Sreeja
authors.forename: Thankayyan R
authors.initials: TR
authors.lastname: Santhosh Kumar
authors.forename: Baddireddi S
authors.initials: BS
authors.lastname: Lakshmi
authors.forename: Sreeharshan
authors.initials: S
authors.lastname: Sreeja
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D005638:Fruit / Q000737:chemistry; D017930:Genes, Reporter; D006801:Humans; D029561:Lythraceae / Q000737:chemistry*; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology; D014162:Transfection
chemical_list: D018931:Antineoplastic Agents, Hormonal; C506487:ESR1 protein, human; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D010936:Plant Extracts; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D004958:Estradiol