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: A Young Kim, Yun Sok Lee, Kang Ho Kim, Jae Ho Lee, Hee Kyu Lee, Su-Hwa Jang, Seong-Eun Kim, Gha Young Lee, Joo-Won Lee, Sung-Ae Jung, Hee Yong Chung, Sunjoo Jeong, Jae Bum Kim
• Journal: Molecular endocrinology (Baltimore, Md.) (Mol Endocrinol) Vol. 24 Issue 7 Pg. 1441-52 (Jul 2010) ISSN: 1944-9917 [Electronic] United States
• PMID: 20444885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Receptors, Adiponectin
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Adiponectin (pharmacology, therapeutic use)
• Animals
• Apoptosis (drug effects)
• Blotting, Western
• CHO Cells
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, metabolism)
• Cricetinae
• Cricetulus
• HCT116 Cells
• HT29 Cells
• Humans
• Polymerase Chain Reaction
• Receptors, Adiponectin (genetics, metabolism)