AMPK inhibitor compound C suppresses cell proliferation by induction of apoptosis and autophagy in human colorectal cancer cells

Weng Lang Yang, William Perillo, Deanna Liou, Philippe Marambaud, Ping Wang

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background and Objectives AMP-activated protein kinase (AMPK) is a main regulator of energy metabolism through the inhibition of biosynthetic pathways and enhancement of ATP-generating pathways. However, targeting AMPK as anti-tumor therapy remains controversial. In this study, we examined the effect of compound C, a small molecule inhibitor of AMPK, on the proliferation of several human colorectal cancer cell lines with diverse characteristics. Methods Four human colorectal cancer cell lines (HCT116, DLD-1, SW480, and KM12C) were treated with compound C. Cell viability was determined by MTS assay. Cell cycle prolife was analyzed by flow cytometry. Acidic vesicular organelles were detected by acridine orange staining. Protein levels were measured by western blotting. Results Compound C inhibited the growth of four cell lines in a dose-dependent manner and caused G2/M arrest. Compound C increased sub-G1 cell population and induced chromatin condensation and cleavage of PARP in HCT116 and KM12C cells, while it induced acidic vesicular formation and conversion of LC3-I to autophagosome-associated LC3-II in DLD-1 and SW480 cells. Survivin, an anti-apoptotic protein, was down-regulated in all cell lines treated with compound C. Conclusions Compound C induces apoptotic or autophagic death in colorectal cancer cells and the preferred death mode is cell type-dependent.

Original languageEnglish (US)
Pages (from-to)680-688
Number of pages9
JournalJournal of Surgical Oncology
Volume106
Issue number6
DOIs
StatePublished - Nov 2012
Externally publishedYes

Keywords

  • AMPK
  • apoptosis
  • autophagy
  • colorectal cancer
  • compound C

ASJC Scopus subject areas

  • Surgery
  • Oncology

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