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Growth inhibition of colon cancer cells by compounds affecting AMPK activity
Michael A Lea1, Jacob Pourat1, Rupali Patel1
1Michael 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.
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.
Insights
Other molecules affecting AMP-dependent protein kinase (AMPK) activity did not mimic metformin
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- AMP-dependent protein kinase (AMPK) is a key regulator of cellular energy metabolism.
- Metformin and phenformin, known AMPK activators, inhibit colon cancer cell proliferation.
- Investigating other AMPK modulators could reveal novel anti-cancer strategies.
Purpose of the Study:
- To evaluate if other molecules modulating AMP-dependent protein kinase (AMPK) activity affect colon cancer cell proliferation and metabolism similarly to metformin and phenformin.
- To compare the effects of various AMPK-affecting compounds on colon cancer cell lines.
Main Methods:
- Four human colon cancer cell lines (Caco-2, HCT116, HT29, SW1116) were used.
- Compounds studied included A-769662, 5-aminoimidazole-4-carboxamide-1-ribofuranoside, butyrate, EGCG, KU-55933, quercetin, resveratrol, and salicylates.
- Measured parameters included cell proliferation, viability, glucose uptake, lactate production, and medium acidification.
Main Results:
- Several AMPK-associated molecules failed to increase medium acidification and glucose uptake in colon cancer cells, unlike metformin and phenformin.
- The observed effect of 5-aminosalicylic acid on glucose levels was an artifact of the assay.
- Compounds were tested at concentrations that inhibited colon cancer cell proliferation.
Conclusions:
- Agents affecting AMP-dependent protein kinase (AMPK) activity inhibit colon cancer cell proliferation without enhancing glucose metabolism.
- This contrasts with the metabolic effects of biguanides like metformin and phenformin.
- The study highlights distinct mechanisms of action for AMPK modulators in colon cancer.
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