Activity of sunitinib analogs on colon cancer cells in wound healing assay

Abstract

Introduction: High mortality from cancer is usually related to late diagnosis and resistance to drugs that cause metastasis. Colon cancer is the second leading cause of death between all cancer types, and 70% of deaths is related to metastasis to liver [1]. No specific drugs have been developed to inhibit metastasis, and only a few anticancer drugs possess antimetastatic effect [2]. There are some evidences that kinase inhibitors could inhibit cancer cell migration [3]. Therefore, the aim of our research was to evaluate the antimigratory activity of sunitinib analogs (#1, #6, #7) synthesized at Cagliari University, Italy. Materials and methods: As a colon cancer model for experiments, we used two colon cancer cell lines HT-29 and HCT116. The effect of compounds was evaluated by using a ‘wound healing’ assay. In this method, the wound is made in the monolayer of cells and the photos are taken at 0, 24, 48 and 72 hours. Then the area of the wound is evaluated in percents. 10%, 50% and 90% of compound concentrations from EC50 value were used in this study. EC50 value represents the concentration of a compound causing 50% reduction of cancer cell metabolic activity that has been established by MTT assay before these experiments. Results: It has been established that HT-29 cells are tempted to migrate faster than HCT116 cells. Overall, all tested compounds inhibited the migration of both cell lines. The most active compound on both cell line migration was #1. It significantly inhibited the migration of cells at 90% of EC50 concentration after 72 h of incubation (p < 0.05). HT-29 cells migrated 1.54 times slower, and HCT116 cells migrated 1.14 times slower compared to the cells in control groups. Other tested compounds #6, #7 and sunitinib did not significantly inhibit migration of HT-29 and HCT116 cells. Conclusions: Sunitinib analog, compound #1 inhibited migration of both cell lines and was more active compared to c[...].