3rd International Congress on Biomedicine (ICB2019)
Ghrelin Induces Autophagy and Expression CXCR4 Via AMPK in Lymphoblastic leukemia Cell lines
Ghrelin Induces Autophagy and Expression CXCR4 Via AMPK in Lymphoblastic leukemia Cell lines
Masoud Heshmati,1Mohammad-Javad Sanaei,2Mahdi GhatrehSamani,3,*
1. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran 2. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran 3. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
Introduction: Acute T cell lymphoblastic leukemia (T-ALL) is a neoplastic disorder of lymphocytes that occurs in children and adults. One of the features of this disease is the infiltration of other organs (metastasis) and the creation of a repertoire of malignant lymphoblasts. The receptor CXCR4 play important roles in the metastasis of this malignancy. One of the important goals of anticancer therapies is to induce cell death and inhibit cell proliferation. Although the treatment improved in the last decades, it is failed in 30% of cases. In the absence of apoptosis, autophagic cell death can be an alternative target for cancer treatment. Ghrelin is a small peptide hormone that in addition to feeling hungry and stimulating the release of growth hormone, it increases autophagy in cancer cells. AMPK (AMP-activated protein kinase) stimulate and inhibit the proteins involved in autophagy, metastasis, and induction of apoptosis. given the importance of elucidating the role of ghrelin and AMPK in induction of proteins involved in autophagy and metastasis, we decided to investigate the effect of these factors on CXCR4 expression and autophagy on Jurkat and Molt4 cell lines.
Methods: Jurkat and Molt4 cells were cultured in RPMI 1640 medium and treated with 10nM ghrelin, 3.7 µM (for 6-hour Jurkat), 3.4 µM (for 24-hour Jurkat), 2.4 µM (for 6-hour Molt-4), 3.1 µM (for 24-hour Molt-4) Compound C (setup by IC50 calculate). Cell proliferation was assessed by MTS assay, induced apoptosis and expression of CXCR4 by flow cytometry and induction of autophagy by western blot After 6 and 24 hours of adding hormones and inhibitors.
Results: The results showed that AMPK expression was upregulated the time-dependent during induction of autophagy by ghrelin in Jurkat and Molt4 cells and was also inhibited by inactivation of Compound C. Our data showed that ghrelin can induce autophagy and CXCR4 in the time-dependent manner.
Conclusion: The results of the present study showed that ghrelin induces autophagy and up-regulation of the CXCR4 expression by AMPK in Jurkat and Molt4 cells. Ghrelin-induced autophagy did not lead to cell death due to the weak apoptosis and proliferation observed at 6 and 24 hr of autophagy.