Breast cancer is one of the most common types of cancer in women and 70 percentage of breast cancer is caused by the over expression of Estrogen receptor (ER). ER represents a viable and important pharmaceutical target against cancer. It is targeted by pharmaceutical agents for hormone replacement in menopausal women and reproductive cancers such as prostate cancer, uterine cancer and breast cancer . ERs are classified into two types, ER alpha and ER beta which belongs to the super family of nuclear receptors. ER alpha and ER beta have similar but not identical structures. Up regulation of ER alpha causes cell proliferation, inhibition of apoptosis, stimulation of invasion and metastasis, and promotion of angiogenesis. While not much is known about ER beta, it is believed that its function is distinct from ER alpha and it probably has opposing activity on tumour growth . Tamoxifen is the drug regularly prescribed for the treatment of breast cancer. The anticancer property of Tamoxifen has been attributed to its anti estrogenic properties. The use of Tamoxifen is limited due to the acquired Tamoxifen resistance in many cancer patients .
Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs which have anti inflammatory action and also used for fever (anti pyretic) and pain reduction. Aspirin is the first NSAIDs used for treating human ailments, which is derived from the bark of the willow tree. NSAIDs act as non selective inhibitors of the enzyme cyclooxygenase (COX) causing the reduction of the formation of prostaglandin and thromboxane. NSAIDs have recently received increasing attention as anticancer agents. In vivo studies with NSAIDs have shown the anticancer property of these drugs against breast cancer . The mechanism of action of NSAIDs as an anticancer agent is due to the inhibition of one or both of the two isoforms of the COX enzymes. Evidence suggests that COX is upregulated in most cancers ; cyclooxygenase-1 is expressed in nearly all cells, and cyclooxygenase-2 is induced during inflammation or by tumour oncogenes and promoters and is over expressed in breast cancers. Use of NSAIDs blocks inflammatory reactions, and may inhibit mutagenesis and angiogenesis and promote apotopsis [6-8].
NSAIDs are classified based on their structure or mechanism of action . In this study one drug is selected randomly from each of these classes. The drugs chosen are Aspirin (Salicylates), Ibuprofen (Propionic acid derivatives), Inodmethacin (Acetic acid derivatives), Mefenamic acid (Fenamic acid derivatives), Nimeuslide (Sulphonanilides), piroxicam(Enolic acid derivatives) and Valdecoxib (selective COX-2 inhibitors).
In silico docking studies are important for deducing protein ligand interaction properties such as hydrogen bond donor acceptor, binding energy, electron distribution, geometry complementarity, hydrophobicity and polarizability. These studies have potential use in the discovery and optimization...