Evaluation of Anticancer and Epidermal Growth Factor Receptor Inhibition Activity by Benzochromeno Pyrimidin Derivatives in Three Human Cancer Cell Lines

Abstract

Background: Cancer therapy is one of the most important challenges that human being faces. The abnormal activity of epidermal growth factor receptor tyrosine kinase (EGFR1) in tumors has been reported in many studies. Tyrosine kinase inhibitors are now commercially available for the treatment of a variety of cancers. Based on our previous studies, we assumed that a hybrid of aminopyrimidine derivatives as EGFR inhibitors and benzocheromen derivatives as cytotoxic agents can induce apoptosis in EGFR positive cancer cells. In the present study, the cytotoxic effect, ability of EGFR inhibition and apoptosis induction of some syndfrthetic benzochromene pyrimidine derivatives were investigated on MDA-MB231, SKBR3 and PC3 cell lines. Methods: The EGFR inhibition activity was determined using cell-based EGFR ELISA kit. Cell viability was determined by MTT assay in 2D and 3D cultures. The apoptosis was confirmed through different methods such as fluorescent staining, annexin V– propidium iodide double staining, DNA-Ladder assay, caspase-3 colorimetric assay, and nitric oxide assay. Results: The Results of the MTT assay showed that derivatives with different substituent exhibited differential cytotoxicity in three cancer cell lines, although in MDA-MB231 the cytotoxicity effect of compounds are more obvious than the other cell lines. Production of nitric oxide, caspase-3 activity and DNA-fragmentation was significant in MDA-MB231 and PC3 cells. SKBR3 cells, despite having the lowest apoptosis among these three cell lines, showed a significant EGFR inhibition in the ELISA assay. Conclusion: In this research we proved that hybrids of benzocheromen and amino pyrimidine could be effective on growth inhibition of cancer cell lines and may be used as a drug candidate for cancer therapy in the future.