Original Article
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World J Gastrointest Oncol. Jul 15, 2014; 6(7): 244-252
Published online Jul 15, 2014. doi: 10.4251/wjgo.v6.i7.244
Growth inhibition of colon cancer cells by compounds affecting AMPK activity
Michael A Lea, Jacob Pourat, Rupali Patel, Charles desBordes
Michael A Lea, Jacob Pourat, Rupali Patel, Charles desBordes, Department of Biochemistry and Molecular Biology, New Jersey Medical School, Rutgers University, Newark, NJ 07103, United States
Charles desBordes, Department of Biology, Medgar Evers College-City University of New York, Brooklyn, NY 11225, United States
Author contributions: Lea MA reviewed the literature, designed the experiments and wrote the initial draft; all authors participated in the data collection, analysis of the results and revision of the draft manuscript.
Supported by The grants from the Alma Toorock Memorial for Cancer Research
Correspondence to: Michael A Lea, PhD, Department of Biochemistry and Molecular Biology, New Jersey Medical School, Rutgers University, 185 South Orange Avenue, Newark, NJ 07103, United States. lea@njms.rutgers.edu
Telephone: +1-973-9725345 Fax: +1-973-9725594
Received: November 17, 2013
Revised: January 17, 2014
Accepted: April 16, 2014
Published online: July 15, 2014
Processing time: 239 Days and 14.4 Hours
Abstract

AIM: To determine if other molecules reported to modulate AMP-dependent protein kinase (AMPK) activity would have effects resembling those of metformin and phenformin on colon cancer cell proliferation and metabolism.

METHODS: Studies were performed with four human colon cancer cell lines, Caco-2, HCT116, HT29 and SW1116. The compounds that were studied included A-769662, 5-aminoimidazole-4-carboxamide-1-ribofuranoside, butyrate, (-)-epigallocatechin gallate (EGCG), KU-55933, quercetin, resveratrol and salicylates. The parameters that were measured were cell proliferation and viability, glucose uptake, lactate production and acidification of the incubation medium.

RESULTS: Investigations with several molecules that have been reported to be associated with AMPK activation (A-769662, 5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside, EGCG, KU-55933, quercetin, resveratrol and salicylates) or AMPK inhibition (compound C) failed to reveal increased medium acidification and increased glucose uptake in colon cancer cells as previously established with metformin and phenformin. The only exception was 5-aminosalicylic acid with which there were apparently lower glucose levels in the medium after incubation for 72 h. Further study in the absence of cells revealed that the effect was an artifact due to inhibition of the enzyme-linked glucose assay. The compounds were studied at concentrations that inhibited cell proliferation.

CONCLUSION: It was concluded that treatment with several agents that can affect AMPK activity resulted in the inhibition of the proliferation of colon cancer cells under conditions in which glucose metabolism is not enhanced, in contrast to the effect of biguanides.

Keywords: Colon cancer cells; Proliferation; AMP-dependent protein kinase; Glucose metabolism

Core tip: Treatment with several agents that can affect AMP-dependent protein kinase activity resulted in the inhibition of the proliferation of colon cancer cells under conditions in which glucose metabolism is not enhanced, in contrast to the effect of biguanides.