AMP-activated kinase (AMPK)-generated signals in malignant melanoma cell growth and survival.
Extensive studies over the years have shown that the AMP-activated kinase (AMPK) exhibits negative regulatory effects on the activation of the mammalian target of rapamycin (mTOR) signaling cascade. We examined the potential involvement of AMPK in the regulation of growth and survival of malignant melanoma cells. In studies using the AMPK activators AICAR or metformin, we found potent inhibitory effects of AMPK activity on the growth of SK-MEL-2 and SK-MEL-28 malignant melanoma cells. Induction of AMPK activity was also associated with inhibition of the ability of melanoma cells to form colonies in an anchorage-independent manner in soft agar, suggesting an important role of the pathway in the control of malignant melanoma tumorigenesis. Furthermore, AICAR-treatment resulted in malignant melanoma cell death and such induction of apoptosis was further enhanced by concomitant statin-treatment. Taken together, our results provide evidence for potent inhibitory effects of AMPK on malignant melanoma cell growth and survival and raise the potential of AMPK manipulation as a novel future approach for the treatment of malignant melanoma.
Woodard
Jennifer
J
Robert H. Lurie Comprehensive Cancer Center, Division of Hematology-Oncology, Northwestern University, Medical School, Jesse Brown VA Medical Center, Chicago, IL 60611, USA.
Platanias
Leonidas C
LC
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D012265:Ribonucleotides / Q000494:pharmacology; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology*
D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide