Abstract
G protein-coupled estrogen receptor (GPER) was reported to be a potential target in the breast cancer therapy. This study aimed to illuminate the function of GPER and its mediated PI3K/AKT pathway in cryptotanshinone (CPT) inducing cell apoptosis and antiproliferation effect on GPER positive breast cancer MCF-7 cells. Cell proliferation was tested by MTT assay. Apoptosis rates were tested by Annexin V-FITC/PI double staining and the cell cycle was researched by flow cytometry. Autodock vina was applied to make molecular docking between CPT or estradiol and GPER. siRNA technique and GPER specific agonist G-1 or antagonist G-15 were applied to verify the mediated function of GPER. Apoptosis and cell cycle related proteins, as well as the key proteins on PI3K/AKT signaling pathway were detected by western blot. The results indicated that CPT could exert antiproliferation effects by arresting cell cycle in G2/M phase and downregulating the expression of cyclin D, cyclin B and cyclin A. Besides, apoptosis induced by CPT was observed. CPT might be a novel GPER binding compounds. Significantly, suppression of PI3K/AKT signal transduction by CPT was further increased by G-1 and decreased by G-15. The study revealed that the effect of antiproliferation and apoptosis treating with CPT on MCF-7 cells might be through the downregulation of PI3K/AKT pathway mediated by activated GPER.
Highlights
Breast cancer is one of the most priority concerns for women around the world and results in relatively high rates of morbidity and mortality [1]
The expression of cyclin D, cyclin B and cyclin A tested by western blot indicated that CPT have an inhibitory effect on cyclins
Since the drug resistance in hormone treatment of breast cancer caused by targeting classic estrogen receptors, the discovery of G protein-coupled estrogen receptor (GPER) brought a new breakthrough point to illustrate the mechanism of the effects of estrogen or estrogenic substances on proliferation and apoptosis process
Summary
Breast cancer is one of the most priority concerns for women around the world and results in relatively high rates of morbidity and mortality [1]. It is estimated that more than 1 million people are diagnosed with breast cancer each year and that at least 400,000 women will die from this disease annually, accounting for 14 per cent of all cancer deaths [2,3]. According to the China National Cancer Center, the incidence of breast cancer has obviously increased more than twice as fast as global rates since 1990s, especially in urban city [4,5].
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