In-silico Drug Design and in-silico screening (Track)
In Silico Analysis Of Flavonoids For Its Estrogen Receptor Binding Activity And Its Effect On Estrogen Receptor (Er) Mediated Pathways: An Vitro Approach In Er Positive Breast Cancer Cell Line
S. Sreeja
Integrated Cancer Research, Rajiv Gandhi Center for Biotechnology, India
Abstract:
The steroid hormone estrogen causes its multitude effects through estrogen receptors (ER) that mediate the transcription of number of genes involved in reproduction, metabolism, growth and differentiation. Chemoprevention targeting ER, by the use of naturally occurring dietary substances is considered as a rational approach to reduce the ever increasing incidence of cancer. Among dietary agents flavonoids are naturally occurring polyphenolic compounds, which exhibit wide range of biological effects. The present study is primarily focused on finding out a potential candidate for chemoprevention from the flavonoid family by in silico analyses and further in vitro studies. These compounds were screened for their binding properties at the active site of ER by molecular docking studies using the GOLD software package. The binding affinity of each flavonoid towards estrogen receptors was scored and receptor ligand interaction was analyzed to provide simulation characteristics of virtual molecular recognition mechanisms. The study revealed the degree of probability of tested compounds to bind to the ER alpha ligand binding domain compared to estradiol (natural ligand) and tamoxifen (partial antagonist). Already reported genistein is showing high affinity to the ER α. It is followed by chrysin, apigenin and luteolin. The conformational change caused by these molecules compared to natural ligand estradiol is quite evident. These three candidate molecules due to its low molecular weight and small size probably may act as antagonists which deserves further in vitro studies. Cell viability and apoptotic studies were carried out to find out the efficacy of these compounds on the growth of estrogen receptor positive breast cancer cell lines. Results from Insilco analysis suggest that these compounds can bind to the estrogen receptor. Our in vitro studies revealed the efficiency of these compounds to inhibit cell proliferation and induce apoptosis in ER positive breast cancer cell line. Further investigation is necessary in order to identify the cellular targets of these compounds and alternative pathways explaining its activity.
