Western Kentucky University

Molecular Level Interaction of an Aminoglycoside Antibiotic with Human Fibroblast Growth Factor 1

Institution

Western Kentucky University

Abstract

Fibroblast growth factors (FGF) work as modulators of different cell activities like mitosis, differentiation, and cell survival. Within the FGF family human FGF-1 is the potent angiogenic factor, involved in the formation of new blood vessels in tissues. Human FGF-1 binds with heparin and forms a binary complex, which further binds to fibroblast growth factor receptors (FGFRs), this binding triggers downstream events involving different cell signaling pathways and ultimately leads to cell proliferation. Human FGF-1 is one of the targets in cancer inhibition and obesity due to its involvement in blood vessel formation in cancerous regions and adipose tissues. Results of recent studies have indicated that there is a decrease in cell proliferation capacity of patients who have been on antibiotics for longer periods. It could be due to interaction of antibiotics with proteins involved in cell proliferation like FGFs. Recently anticancer activity of an antibiotic called Lidamycin, which is an aminoglycoside, was noticed in cancer cell lines. Antibiotics like aminoglycosides have resemblance in their molecular structure with heparin, hence the amino glycosides can compete with the heparin in order to bind with the hFGF-1and these interactions may affect the normal cell proliferation process. On the basis of above experimental studies and associated hypothesis, we designed a project to study the interaction between hFGF-1 and kanamycin, which is an aminoglycoside antibiotic.

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Molecular Level Interaction of an Aminoglycoside Antibiotic with Human Fibroblast Growth Factor 1

Fibroblast growth factors (FGF) work as modulators of different cell activities like mitosis, differentiation, and cell survival. Within the FGF family human FGF-1 is the potent angiogenic factor, involved in the formation of new blood vessels in tissues. Human FGF-1 binds with heparin and forms a binary complex, which further binds to fibroblast growth factor receptors (FGFRs), this binding triggers downstream events involving different cell signaling pathways and ultimately leads to cell proliferation. Human FGF-1 is one of the targets in cancer inhibition and obesity due to its involvement in blood vessel formation in cancerous regions and adipose tissues. Results of recent studies have indicated that there is a decrease in cell proliferation capacity of patients who have been on antibiotics for longer periods. It could be due to interaction of antibiotics with proteins involved in cell proliferation like FGFs. Recently anticancer activity of an antibiotic called Lidamycin, which is an aminoglycoside, was noticed in cancer cell lines. Antibiotics like aminoglycosides have resemblance in their molecular structure with heparin, hence the amino glycosides can compete with the heparin in order to bind with the hFGF-1and these interactions may affect the normal cell proliferation process. On the basis of above experimental studies and associated hypothesis, we designed a project to study the interaction between hFGF-1 and kanamycin, which is an aminoglycoside antibiotic.