AIM:To determine if other molecules reported to modulate AMP-dependent protein kinase(AMPK)activ-ity would have effects resembling those of metformin and phenformin on colon cancer cell proliferation and metabolism.METHODS:Studies were performed with four hu-man colon cancer cell lines,Caco-2,HCT116,HT29 and SW1116.The compounds that were studied included A-769662,5-aminoimidazole-4-carboxamide-1-ribofu-ranoside,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 activa-tion(A-769662,5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside,EGCG,KU-55933,quercetin,resve-ratrol and salicylates)or AMPK inhibition(compound C)failed to reveal increased medium acidification and increased glucose uptake in colon cancer cells as previ-ously established with metformin and phenformin.The only exception was 5-aminosalicylic acid with which there were apparently lower glucose levels in the me-dium 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. AIM: To determine if other molecules reported to modulate AMP-dependent protein kinase (AMPK) activ-ity would have effects resembling those of metformin and phenformin on colon cancer cell proliferation and metabolism. METHODS: Studies were performed with four hu-man colon cancer Cell lines Caco-2, HCT116, HT29 and SW1116.The compounds that were studied included A-769662, 5-aminoimidazole- 4-carboxamide- 1-ribofu ranoside, butyrate, (-) - epigallocatechin gallate (EGCG) -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 activa tion (A-769662, 5-aminoimidazole-4-carboxamide-1-bD-ribofuranoside, EGCG, KU- 55933, quercetin, resve- ratrol and salicylates) or AMPK inhibition (compound C) failed to reveal increased medium acidification and increased glucose uptake in colon cance r cells as previ-ously established with metformin and phenformin. The only exception was 5-aminosalicylic acid with which there were apparently lower glucose levels in the me-dium after incubation for 72 h. Future 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.