Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway.
Adiponectin is a peptide hormone secreted by adipose tissue. It is a key hormone responsible for insulin sensitization, and its circulating level is inversely associated with abdominal obesity. Recent studies have shown that a reduced plasma adiponectin level is significantly correlated with the risk of various cancers. However, there are few studies regarding the association of adiponectin and colorectal cancer. To address this issue, we investigated the effect of adiponectin on colorectal cancer cells. Three colorectal cancer cell lines express both AdipoR1 and AdipoR2 receptors. MTT assay revealed that adiponectin inhibited human colorectal cancer cell growth. Furthermore, Western blot analysis revealed that adiponectin activated adenosine monophosphate-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR) pathways. Selective AMPK inhibitor compound C abrogated the inhibitory effect of adiponectin on cell growth. Our results clearly demonstrate the novel findings that adiponectin inhibits colorectal cancer cell growth via activation of AMPK, thereby down-regulating the mTOR pathway.
Sugiyama
Michiko
M
Division of Gastroenterology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan.
Takahashi
Hirokazu
H
Hosono
Kunihiro
K
Endo
Hiroki
H
Kato
Shingo
S
Yoneda
Kyoko
K
Nozaki
Yuichi
Y
Fujita
Koji
K
Yoneda
Masato
M
Wada
Koichiro
K
Nakagama
Hitoshi
H
Nakajima
Atsushi
A
D000230:Adenocarcinoma / Q000473:pathology*; D000263:Adenylate Kinase / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D006706:Homeostasis; D006801:Humans; D011494:Protein Kinases / Q000502:physiology*; D054419:Receptors, Adiponectin / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases
D052242:Adiponectin; D054419:Receptors, Adiponectin; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase