Adiponectin and metformin additively attenuate IL1b-induced malignant potential of colon cancer

Hyun Seuk Moon, Christos S. Mantzoros

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Both adiponectin (AD) and metformin (Met) have been proposed to downregulate cell proliferation of colon cancer cells, but whether their effect might be additive has not been studied to date. Genetic studies in humans have suggested an important role for interleukin 1b (IL1b) in cancer pathogenesis. Direct evidence that IL1b contributes to the development of colon cancer has not yet been fully confirmed and no previous studies have evaluated how IL1b may interact with AD and/or Met to regulate malignant potential and intracellular signaling pathways in human and mouse colon cancer cells. We conducted in vitro studies using human (LoVo) and mouse (MCA38) colon cancer cell lines to evaluate whether AD and Met alone or in combination may antagonize IL1b-regulated malignant potential in human and mouse colon cancer cell lines. IL1b increased malignant potential and regulated the expression of tumor suppressor (p53) and cell cycle regulatory genes (p21, p27, and cyclin E2) in human and mouse colon cancer cell lines. These effects were reversed by co-Administration of AD and/or Met and were additively altered by AD and Met in combination in a STAT3- and AMPK/LKB1-dependent manner. We also observed using fluorescence activated cell sorter analysis that IL1b-regulated cell cycle progression is altered by AD and Met alone or in combination. Our novel mechanistic studies provide evidence for an important role for IL1b in colon cancer and suggest that AD and/or Met might be useful agents in the management or chemoprevention of IL1b-induced colon carcinogenesis.

Original languageEnglish
Pages (from-to)849-859
Number of pages11
JournalEndocrine-Related Cancer
Volume20
Issue number6
DOIs
Publication statusPublished - 2013 Dec

Keywords

  • Adiponectin
  • Colon cancer
  • Interleukin 1b
  • Lkb1
  • Malignant potential
  • Metformin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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