The Antiangiogenic Effects of Tamoxifen might be Attributed to Receptor Binding Capacity of its Solvent Dimethylsulfoxide in Breast Cancer: A Molecular Docking Study
Orhan Koçak *
Department of Biology, Graduate School of Natural and Applied Sciences, Akdeniz University, 07058, Campus, Antalya, Turkey.
Nazlı Deniz Taşkın
Department of Neuroscience, Mcgill University, Canada.
Ece Şimşek
Department of Nutrition and Dietetics, Faculty of Health Sciences, Akdeniz University, 07058, Campus, Antalya, Turkey.
*Author to whom correspondence should be addressed.
Abstract
Aim: Tamoxifen, a Dimethyl sulfoxide (DMSO)-soluble chemotherapeutic, is widely used in the treatment of breast cancer. Tamoxifen has an anti-angiogenic effect especially on breast tumor cells by blocking VEGF(Vascular Endothelial Growth Factor) production. On the other hand, according to our previously studies, we demonstrated that DMSO could mimics the cytotoxic effects of Thalidomide in 4T1 mouse breast cancer cells and is related with the anti-angiogenic response of HeLa cells. At this point of view, the aim of this study was to determine the possible binding effects of DMSO on certain cell surface receptors.
Methods: The in silico studies were implemented using the Docking Server. X-ray structures of receptor proteins’ PDB files were obtained from Protein Data Bank [Human Progesteron Receptor (PDB ID: 1A28, Human Tumor Necrosis Factor Receptor-1 (PDB ID: 1EXT), Human Interferon Gamma Receptor-1 (PDB ID: 1FG9), Human Epidermal Growth Factor Receptor (PDB ID: 1IVO)]. Docking simulations were performed using the Lamarckian genetic algorithm (LGA) and the Solis & Wets local search method.
Results: According to the molecular docking results of this study, DMSO, the general solvent of Tamoxifen, has a 90% binding capacity to the Interferon Gamma (IFNɣ) receptor and 100% to Tumor Necrosis Factor alfa (TNFα) receptor, respectively.
Conclusion: These receptors have significant effects on the proliferation and angiogenesis of cancer cells which leads to the metastasis of breast cancer. In conclusion, the antiangiogenic effects of Tamoxifen might be reduced due to its solvent DMSO's angiogenic effects.
Keywords: Tamoxifen, DMSO, IFNɣ, TNFα, molecular docking, angiogenesis, breast cancer.