Abstract
13C NMR isotopomer analysis was used to characterize intermediary metabolism in three colorectal cancer cell lines (WiDr, LS1034, and C2BBe1) and determine the “metabolic remodeling” that occurs under hypoxia. Under normoxia, the three colorectal cancer cell lines present high rates of lactate production and can be seen as “Warburg” like cancer cells independently of substrate availability, since such profile was dominant at both high and low glucose media contents. The LS1034 was the less glycolytic of the three cell lines and was the most affected by the event of hypoxia, raising abruptly glucose consumption and lactate production. The other two colorectal cell lines, WiDr and C2BBe1, adapted better to hypoxia and were able to maintain their oxidative fluxes even at the very low levels of oxygen. These differential metabolic behaviors of the three colorectal cell lines show how important an adequate knowledge of the “metabolic remodeling” that follows a given cancer treatment is towards the correct (re)design of therapeutic strategies against cancer.
Highlights
Cancer cell alters its metabolism in response to a challenging environment by promoting cell growth and proliferation, diverging significantly from normal tissues
After this period there is a considerable reduction in lactate production which is consistent with a significant reduction in glucose levels in the culture media
The three cell lines exhibit a very pronounced glycolytic metabolic profile, exporting considerable amounts of lactate to the culture media. This “Warburg” like metabolic behavior is characteristic of many tumor cells and was expectable for the colorectal cancer cell lines under study
Summary
Cancer cell alters its metabolism in response to a challenging environment by promoting cell growth and proliferation, diverging significantly from normal tissues. Metabolism in “Warburg” like tumor cells could at first be seen as “wasteful” when compared to normal cells, or we could say that tumor cells use a disproportionate nutrient exchange with its environment. This metabolic profile is prevalent in many cancer cells and grants them advantage over normal cells by allowing them to proliferate at much higher rates. The regulation of glycolysis by these enzymes allows the alterations in glycolytic fluxes required to fulfill cancer cells bioenergetics and biosynthetic demands.
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