Selective estrogenic activity of Gouania longipetala Hemsl. (Rhamnaceae) aqueous extract through in vivo and in vitro antiproliferative approaches on MCF-7-167 and MDA-MB-231 cancer cells.

[BACKGROUND AND AIM] Estrogens used in hormone therapy could lead to some cancers on uterus and mammary gland. Due to estrogenic activity, Gouania longipetala (GLO), is used to manage climacteric complaints and postmenopausal disorders. The present study aimed to assess mechanisms supporting GLO's activity on estradiol-sensitive tissues in vivo and, on breast cancer cells in vitro. The study was also about to characterize and identify Gouania longipetala active compounds.

[METHODOLOGY] Distilled water, estradiol and 45 and 180 mg/kg doses of G. longipetala, were orally administrated over 3 days to ovariectomized rats. Morphometric analyses were performed on vagina, uterus and breast. Then, a wide range of doses of G. longipetala was used to study the effects on MDA-MB-231 and MCF-7-167 cell proliferation. Binding to estrogen receptors was performed using transfection assay and, cell cycle was studied in MCF-7-167 cells using flow cytometry. Real-time PCR was assessed to quantify PgR, pS2, GREB1, CXCL12 and AREG gene expression. GLO phytochemicals were identified using liquid chromatography-mass spectrometry (LC-MS) analyses.

[RESULTS] G. longipetala induced vaginal epithelial cell proliferation in ovariectomized rats, without significant activity on uterus and mammary gland. In vitro, GLO extract showed a powerful antiproliferative activity on MCF-7-167 and MDA-MB-231 cells, and even on E2-induced proliferation of MCF-7-167 cells, probably due to kaempferol-3-O-a-L-rhamnopyranoside, identified in the plant extract. GLO showed a slight involvement of binding to estradiol receptors and, decreased particularly PgR, GREB1 and CXCL12 E2-induced gene expression.

[CONCLUSION] Overall, Gouania longipetala aqueous extract exhibit selective activity on estradiol-sensitive tissues in vivo and, various effects against breast cancer cell proliferation and estradiol-induced proliferative effects in vitro. All taken into account, GLO may have a notably importance as therapeutic agent used in chemotherapy against E2-dependent cancer.