In Silico and In Vitro Studies Evidenced Antcancer Natural Compounds, a Targetng Chemokine Receptor Singh Pushpendra and Felix Bast Centre for Biosciences, Central University of Punjab, Bathinda, Punjab, India Corresponding author: Singh Pushpendra, Centre for Biosciences, Central University of Punjab, Bathinda, Punjab, India, Tel: 9569330844; E- mail: pushsingh02@gmail.com Received: 04 October 2016; Accepted: 15 November 2016; Published: 19 November 2016; Citaton: Pushpendra S, Bast F. In Silico and in Vitro Studies Evidenced Antcancer Natural Compounds, a Targetng Chemokine Receptor. Ann Clin Lab Res. 2016, 4: 4. Abstract Chemokines are a family of small chemotactc cytokines, which play a signifcant role in lymphocyte homing to secondary lymphoid organs in additon to tumor growth and metastasis. Thus, inhibiton of chemokine receptor caught atenton for antcancer treatment strategy. We studied molecular docking of chemokines receptor CXCR2, CXCR4, and CCR5 against natural and marine compounds. All selected natural and marine compounds were docked with the X-ray crystal structure of CXCR2, CXCR4, and CCR5 retrieved from the PDB by using Maestro 9.6. Molecular docking was executed by the XP (extra precision) mode of GLIDE. On the basis of Gscore and protein-ligand interactons, top-ranking compounds were outlined. The docking study carried out to summarize the various Gscore, hydrophobic, electrostatc bond, hydrogen bond, π-caton and π-π interactons and oversee the protein-ligand interactons. Moreover, efect of Epigallocatechin-3-gallate (EGCG) on biological actvity such as mRNA expression (CXCR2, CCR5, and Bid), cell proliferaton, ROS, and cell-migraton was reported afer the 48 hrs treatments in MCF-7 cells. The RT-PCR densitometric bands analysis showed that compound EGCG reduced the mRNA expression of CXCR2, CCR5 and increased the Bid at 40 µM and 80 μM concentraton. Moreover, EGCG signifcantly reduced cell proliferaton, ROS generaton and cell-migraton afer 48 hours treatments. Keyword: Cancer, Chemokines, Natural and marine compounds, Maestro 9.6, Molecular docking, In vitro Introducton Chemokines are a family of proteins that comprises 44 members in humans, which have a propensity for the migraton of cells. Chemokines and their receptors, contributed a signifcant role in physiological functons such as responses, allowing lymphocyte maturaton, cell survival, cell proliferaton, and cell-migraton, these movement engaged in cancer initaton, angiogenesis, tumor growth, and metastasis. The overexpression of chemokine receptors by blood cancer and solid tumors augment the possibility of cancer initaton and progression [1]. CXCR2 predominant chemokine receptor has been implicated in many cancers including melanoma, breast, prostate, renal, pancreatc, and esophageal cancer. Targetng CXCR2 enhances chemotherapeutc response, inhibits the angiogenesis, and metastasis of breast cancer [2,3]. CXCR4 is the prime chemokine receptor has been alarmed in many cancers including melanoma, breast, ovarian, prostate, pancreatc, colorectal, renal, osteosarcoma, NSCLC, AML, ALL, multple myeloma [4,5]. Moreover, CXCR2, CXCR4 and CCR5 has a key role in fundamental aspects of cancer, including proliferaton, migraton, invasion, and angiogenesis [6,7]. Ziconotde, a peptde discovered from marine tropical cone snail, was approved in the United States in December 2004 for the treatment of Prialt (Elan Pharmaceutcals). Moreover, in October 2007, trabectedin (Yondelis; Pharma Mar) became the frst marine antcancer drug that was approved in the European Union [8]. Monoclonal antbodies against CXCR2, CXCR4 and CCR5, have entered into clinical trials for cancer therapy including MLN1202 and plerixafor [9,10]. Monoclonal antbodies relatvely have beter optons due to their long half-life in blood, their ability to establish concrete and high-afnity interactons with immune cells, together with their comparatvely low toxicity. But on the other hand, drugs from monoclonal antbodies difcult and expensive to develop, in additon to less convenient to administer than small molecule drugs. Inhibitng the chemokine ligands/receptors interactons present on the tumor cells ensued as a new therapeutc approach. MariaVela 2015 reported that CXCR2, CXCR4, and CCR5 chemokine are most actvated chemokine during the metastases in various cancer including melanoma, breast cancer, ovarian cancer, prostate cancer, glioma, neuroblastoma, squamous cell cancer, head and neck cancer [1]. In this context, receptor-based molecular docking was performed to identfy multtargeted inhibitor for chemokine receptor. Research Article iMedPub Journals http://www.imedpub.com/ DOI: 10.21767/2386-5180.1000133 Annals of Clinical and Laboratory Research ISSN 2386-5180 Vol.4 No.4:133 2016 © Copyright iMedPub | This article is available from: http://www.aclr.com.es/ 1