Abstract
This study aimed to investigate the anti-tumor effects of compound 34 on MCF-7 cells in vitro, and explore its mechanisms. MTT results showed that compound 34 selectively inhibited estrogen receptor-positive cells proliferation. Hoechst 33342 staining showed nuclear pyknosis, nuclear debris associated with apoptotic bodies. JC-1 staining showed the loss of mitochondrial membrane potential. Although compound 34 increased intracellular reactive oxygen species (ROS), compound 34-induced apoptosis was not prevented by pretreatment with ROS scavengers. Western blotting showed apoptosis-related protein like cytochrome c and cleaved PARP protein increased. Furthermore, docking studies exhibited that compound 34 could bind into ERα. In summary, compound 34 selectively inhibited estrogen receptor positive cells proliferation and induced apoptosis in MCF-7 cells via ROS-independent intrinsic apoptosis in MCF-7 cells. It may be a potential targeted drug of estrogen receptor for therapeutic application of breast cancer.
 Video Clip of Methodology:
 Assay of Cell Proliferation: 5 min 5 sec Full Screen Alternate
Highlights
IntroductionThe estrogen receptor is overexpressed in 70% of breast cancers
Breast cancer is one of the common diseases among women
Hoechst 33342 were purchased from the Sigma Chemical Co., USA. β-actin, cytochrome c, Bax, Bcl-2 and caspase-3 antibodies were purchased from the Santa Cruz Biotechnology USA; HRP-labelled goat antirabbit IgG antibody and HRP-labeled goat anti-mouse IgG antibody were from the Hua'an Bio (Hangzhou, China); 1-StepTM Ultra TMB-blotting solution was from the Invitrogen (Thermo Fisher Scientific, USA)
Summary
The estrogen receptor is overexpressed in 70% of breast cancers. When the estrogen receptor is activated by estrogen, it is transferred to the nucleus and binds to DNA to regulate gene expression (Helguero et al, 2005). Breast cancer endocrine targeted therapy is to block the binding between estrogen and estrogen receptors, thereby affecting the cell signal transduction and gene transcription to inhibit tumors. As the first FDA-approved estrogen receptor modulator, significantly extends the survival of breast cancer (ER+) patients (Jordan, 1995; Jordan, 2003). 30-40% of breast cancer patients develop resistance after taking 3-5 years of tamoxifen, which affects the prognosis of patients (Merenbakh-Lamin et al, 2013; Robinson et al, 2013; Toy et al, 2013). It is important to develop new estrogen receptor inhibitors to overcome the drug resistance problem (Ciruelos Gil, 2014)
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