Melatonin stimulates HSP27 phosphorylation in human pancreatic carcinoma cells (PANC-1).
Heat shock protein 27 (HSP27) is a cytoprotective chaperone, activated by stressful stimuli. HSP27 modulates aggregation and degradation of many proteins. Recent evidence suggests that HSP27 could be involved in the progression of tumor growth and in the development of resistance of various tumors to chemo- and radiotherapy. It has been reported that melatonin protects pancreatic cells and various tissues against inflammatory damage. Previous experimental studies have shown that melatonin stimulates pancreatic enzyme secretion and improves the outcome of experimental pancreatitis. To investigate whether melatonin could affect HSP27 protein level in human pancreatic carcinoma cells (PANC-1). PANC-1 cells were incubated in the standard medium DMEM supplemented with 10% fetal bovine serum at 37 degrees C with 5% CO2 and humidified atmosphere under basal conditions or in the presence of decreasing doses of melatonin (10(-6) - 10(-12)M). Control experiments were performed with the vehicle only (0,1% DMSO) without melatonin. After 24 h and 48 h the cells were harvested, the cytoplasmic and nuclear proteins were isolated for western blot and immunoblotting studies. Incubation of the PANC-1 cells with melatonin resulted in the stimulation both cytoplasmic and nuclear nonphosphorylated HSP27 protein levels after 24 h of incubation, however, above pools of nonphosphorylated chaperone protein levels were strongly diminished after subsequent 24 h. These changes were accompanied by marked rise of nuclear phosphorylated HSP27. The significant increase of this nuclear protein was observed after 48h of incubation.


CONCLUSIONS
Melatonin stimulates phosphorylation of HSP27 in human pancreatic carcinoma cells (PANC-1).
Leja-Szpak
A
A
Department of Medical Physiology, Faculty of Health Care, Jagiellonian University College of Medicine, Cracow, Poland.
Jaworek
J
J
Szklarczyk
J
J
Konturek
S J
SJ
Pawlik
W W
WW
D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors
D000975:Antioxidants; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D008550:Melatonin