Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation.
In obesity, dysregulation of adipocytokines is involved in several pathological conditions including diabetes and certain cancers. As a member of the adipocytokines, adiponectin plays crucial roles in whole-body energy homeostasis. Recently, it has been reported that the level of plasma adiponectin is reduced in several types of cancer patients. However, it is largely unknown whether and how adiponectin affects colon cancer cell growth. Here, we show that adiponectin suppresses the proliferation of colon cancer cells including HCT116, HT29, and LoVo. In colon cancer cells, adiponectin attenuated cell cycle progression at the G(1)/S boundary and concurrently increased expression of cyclin-dependent kinase inhibitors such as p21 and p27. Adiponectin stimulated AMP-activated protein kinase (AMPK) phosphorylation whereas inhibition of AMPK activity blunted the effect of adiponectin on the proliferation of colon cancer cells. Furthermore, knockdown of adiponectin receptors such as AdipoR1 and AdipoR2 relieved the suppressive effect of adiponectin on the growth of colon cancer cells. In addition, adiponectin repressed the expression of sterol regulatory element binding protein-1c, which is a key lipogenic transcription factor associated with colon cancers. These results suggest that adiponectin could inhibit the growth of colon cancer cells through stimulating AMPK activity.
Kim
A Young
AY
Department of Biophysics and Chemical Biology, School of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul 151-742, Korea.
Lee
Yun Sok
YS
Kim
Kang Ho
KH
Lee
Jae Ho
JH
Lee
Hee Kyu
HK
Jang
Su-Hwa
SH
Kim
Seong-Eun
SE
Lee
Gha Young
GY
Lee
Joo-Won
JW
Jung
Sung-Ae
SA
Chung
Hee Yong
HY
Jeong
Sunjoo
S
Kim
Jae Bum
JB
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D016133:Polymerase Chain Reaction; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*
D052242:Adiponectin; D054419:Receptors, Adiponectin; D055372:AMP-Activated Protein Kinases
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