Antidiabetic exendin-4 activates apoptotic pathway and inhibits growth of breast cancer cells

Exendin-4 is a GLP-1 analog used for the treatment of type 2 diabetes mellitus in its synthetic form. As women with diabetes have higher breast Cancer incidence and mortality, we examined the effect of the incretin drug exendin-4 on breast Cancer cells. The aim of the study is to investigate Anticancer mechanism of exendin-4 in MCF-7 breast Cancer cells. Cytotoxic effects of exendin-4 were determined by XTT assay. IC50 dose in MCF-7 cells were detected as 5 μM at 48th hour. Gene messenger RNA (mRNA) expressions were evaluated by Real-Time PCR. According to results, caspase-9, Akt, and MMP2 expression was reduced in dose group cells, compared with the control group cells. p53, Caspase-3, Caspase-8, Caspase-10, BID, DR4, DR5, FADD, TRADD, PARP, PTEN, PUMA, NOXA, APAF, TIMP1, and TIMP2 expression was increased in dose group cells, compared with the control group cells. Effects of exendin-4 on cell invasion, colony formation, and cell migration were detected by Matrigel chamber, colony formation assay, and wound-healing assay, respectively. To conclude, it is thought that exendin-4 demonstrates anticarcinogenesis activity by effecting Apoptosis, invasion, migration, and colony formation in MCF-7 cells. Exendin-4 may be a therapeutic agent for treatment of breast Cancer as single or in combination with other agents. More detailed researches are required to define the pathways of GLP-1 effect on breast Cancer cells because of the Molecular Biology of breast Cancer that involves a complex network of interconnected signaling pathways that have role in cell growth, survival, and cell invasion.