title: Antidiabetic exendin-4 activates apoptotic pathway and inhibits growth of breast cancer cells.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
authors.forename: Güzin
authors.initials: G
authors.lastname: Fidan-Yaylalı
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey. yavuzdodurga@gmail.com.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Dodurga
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
authors.forename: Mücahit
authors.initials: M
authors.lastname: Seçme
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
authors.forename: Levent
authors.initials: L
authors.lastname: Elmas
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D000077270:Exenatide; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D010455:Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide
keywords: Breast cancer; Diabetes; Exendin-4; Glucagon-like peptide