title: Evidence of pomegranate methanolic extract in antagonizing the endogenous SERM, 27-hydroxycholesterol.
abstract: The direct relationship between obesity and breast cancer has been elucidated recently with the identification of a cholesterol derivative 27-hydroxycholesterol (27HC), an endogenous SERM that can act through estrogen receptor (ER)-mediated mechanisms. Our recent research shed light on the possible SERM-like property of methanol extract of pericarp of pomegranate (PME) by using human breast (MCF-7, MDA-MB-231), endometrial (HEC-1A), cervical (SiHa, HeLa), ovarian (SKOV3) cancer cell lines, normal breast fibroblasts (MCF-10A) and also by in vivo models (ovariectomized Swiss albino mice). Our findings demonstrated that PME binds to ER and downregulates the Estrogen response elements (ERE)-mediated transcription in breast cancer cells without being agonistic in the uterine endometrium and has cardioprotective effects comparable to that of 17-β-estradiol. This preliminary work indicates the ability of PME to antagonize the activity of 27HC. We hypothesize that PME can compete with 27HC for ERα and reduce 27HC-induced proliferation of MCF-7 cells. Relevant estrogen-regulated genes such as pS2, PR and ERα were checked to evaluate the ability of PME to abrogate 27HC-induced genes. This study is significant, being the first report describing that bioactive components of the methanolic extract of pericarp of PME, a proven SERM could plausibly compete for 27HC.
authors.affiliation: Cancer Research Program, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Ravindran
authors.identifier: http://orcid.org/0000-0002-4756-3674
authors.initials: R
authors.lastname: Vini
authors.affiliation: Cancer Research Program, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Azeez M
authors.initials: AM
authors.lastname: Juberiya
authors.affiliation: Cancer Research Program, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Sreeharshan
authors.initials: S
authors.lastname: Sreeja
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry; D061986:MCF-7 Cells; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D006888:Hydroxycholesterols; D010936:Plant Extracts; C076996:27-hydroxycholesterol
keywords: 27-hydroxycholesterol; SERM; breast cancer; obesity; pomegranate