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Evidence of pomegranate methanolic extract in antagonizing the endogenous SERM , 27‐hydroxycholesterol
Author(s) -
Vini Ravindran,
Juberiya Azeez M,
Sreeja Sreeharshan
Publication year - 2016
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1465
Subject(s) - estrogen receptor , chemistry , selective estrogen receptor modulator , estrogen , endogeny , cancer research , in vivo , medicine , pharmacology , endocrinology , breast cancer , biochemistry , cancer , biology , microbiology and biotechnology
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. © 2016 IUBMB Life, 68(2):116–121, 2016