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-b-estradiol. This preliminary work indicates the ability of PME to antagonize the activity of 27HC. We hypothesize that PME can compete with 27HC for ERa and reduce 27HC-induced proliferation of MCF-7 cells. Relevant estrogen-regulated genes such as pS2, PR and ERa 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. V C 2016 IUBMB Life, 68(2): [116][117][118][119][120][121] 2016

The oncogenic roles of 27‑hydroxycholesterol in glioblastoma

“…In mouse models evaluating MCF-7 ×enografts in ovariectomized animals, 27-HC administration results in increased circulating 27-HC concentrations and increased tumor volume (4,7), whereas growth is halted following 27-HC withdrawal (4). Modulation of 27-HC has been proposed as a potential therapeutic method for breast cancer (4,7), with studies investigating 27-HC antagonism ongoing in breast cancer cell lines (8). However, to the best of our knowledge, the effect of 27-HC has not been studied in glioblastoma.…”

Anticancer Activity ofPunica granatum(Pomegranate): A Review

“…Methanol extract of pericarp of pomegranate (PME) binds to ER and causes downregulation of the estrogen response element-mediated transcription in breast cancer lines. Moreover, PME can antagonize 27-hydroxycholesterol (an endogenous SERM associated with postmenopausal breast cancer) activity (Vini et al, 2016). Pomegranate extract (PE) can halt the abnormal multiplication of MCF-7 breast cancer cells as well as induce apoptosis in MCF-7 cell line.…”

Possible use of Punica granatum (Pomegranate) in cancer therapy

“…Furthermore, PME was found to be associated with the ER and caused abrupt expression of estrogen response elements (ERE) [81]. It has also been reported that PME suppressed ER-positive breast tumor growth and proliferation via SERMs [82].…”

“…This aromatase enzyme has been found to play a crucial role in tumorigenesis and takes part in the conversion of androgen to estrogen [78,79]. 27hydroxycholesterol (27HC), an endogenous selective estrogen receptor (ER) modulator (SERM), which is a primary metabolite of cholesterol and an ER and liver X receptor (LXR) ligand, has been found to be responsible for ER-dependent growth in breast cancer [80,81]. The methanolic extract of the pomegranate pericarp (PME) down-regulated the activity of 27HC and led to reduced cell growth and proliferation of breast cancer cells.…”