TY - JOUR
T1 - AMP-activated kinase (AMPK)-generated signals in malignant melanoma cell growth and survival
AU - Woodard, Jennifer
AU - Platanias, Leonidas C.
N1 - Funding Information:
This work was supported by National Institutes of Health grants R01CA121192, R01CA77816, and by a Merit Review grant from the Department of Veterans Affairs (to LCP). JW was supported by a NIH training grant T32CA009560.
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - 5-Aminoimidazole-4-carboxamide riboside (AICAR)
KW - AMP-activated kinase (AMPK)
KW - Malignant melanoma
KW - Metformin
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U2 - 10.1016/j.bbrc.2010.06.052
DO - 10.1016/j.bbrc.2010.06.052
M3 - Article
C2 - 20599746
AN - SCOPUS:77954761710
SN - 0006-291X
VL - 398
SP - 135
EP - 139
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -