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

Autor: Mücahit Seçme, Levent Elmas, Guzin Fidan-Yaylali, Yavuz Dodurga
Rok vydání: 2015
Předmět:
0301 basic medicine
caspase 8 gene
cancer inhibition
XTT assay
venom
Apoptosis
IC50
TRADD gene
FADD gene
MCF-7 cell line
0302 clinical medicine
Breast cancer
caspase 9 gene
cell motion
oncogene
Cell Movement
Cytotoxic T cell
FADD
antineoplastic agent
cancer cell
biology
messenger RNA
caspase 10 gene
Diabetes
Cell migration
General Medicine
PUMA gene
peptide
caspase 3 gene
RNA isolation
female
priority journal
real time polymerase chain reaction
030220 oncology & carcinogenesis
APAF gene
MCF-7 Cells
Female
signal transduction
Signal Transduction
medicine.medical_specialty
Cell Survival
Glucagon-like peptide
PARP gene
Breast Neoplasms
colony formation
Article
03 medical and health sciences
DR5 gene
TIMP1 gene
Internal medicine
Cell Line
Tumor
medicine
spectrophotometry
Anticarcinogenic Agents
Humans
controlled study
human
gelatinase A
Cell Proliferation
Matrigel
BID gene
Cell growth
Exendin-4
Venoms
exendin 4
human cell
tumor cell line
Akt gene
enzyme activation
PTEN gene
medicine.disease
TRADD
NOXA gene
TIMP2 gene
MMP2 gene
030104 developmental biology
Endocrinology
drug effects
biology.protein
Cancer research
DR4 gene
Exenatide
Peptides
metabolism
Zdroj: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 37(2)
ISSN: 1423-0380
Popis: 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. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Databáze: OpenAIRE
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