title: Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation.
abstract: 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.
authors.affiliation: Department of Biophysics and Chemical Biology, School of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul 151-742, Korea.
authors.forename: A Young
authors.initials: AY
authors.lastname: Kim
authors.forename: Yun Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: Kang Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Hee Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Su-Hwa
authors.initials: SH
authors.lastname: Jang
authors.forename: Seong-Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Gha Young
authors.initials: GY
authors.lastname: Lee
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sung-Ae
authors.initials: SA
authors.lastname: Jung
authors.forename: Hee Yong
authors.initials: HY
authors.lastname: Chung
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Jeong
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: 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*
chemical_list: D052242:Adiponectin; D054419:Receptors, Adiponectin; D055372:AMP-Activated Protein Kinases
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