Were Linus Pauling’s views on the anti-cancer benefits of vitamin C megadoses co

Question

Were Linus Pauling’s views on the anti-cancer benefits of vitamin C megadoses correct after all? A recent Science report from the Cantley lab shows that the oxidized form of vitamin C, dehydroascorbic acid, (DHA) selectively kills colon cancer cells whose growth is “driven” by either KRAS (e.g., RasD) or BRAF (e.g., BRAFV600E) oncogenes. What enables DHA to be selectively targeted into these cancer cells and what explains its cytotoxicity?

A. DHA is endocytosed into these cells after binding EGF receptors. DHA increases levels of cytosolic reduced glutathione (GSH) thereby reducing levels of reactive oxygen species (ROS). Reduced ROS inhibits glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which in turn inhibits glycolysis and ATP production and results in cell death.

B. DHA is selectively transported into these cells by overexpressed GLUT1 transporters. DHA depletes cytosolic reduced glutathione (GSH) generating reactive oxygen species (ROS) that inhibit glyceraldehyde 3-phosphate dehydrogenase (GAPDH), thereby inhibiting glycolysis and ATP production and resulting in cell death.

C. DHA is transported into the cells by overexpressed GLUT1 transporters. DHA depletes cytosolic reduced glutathione (GSH) reducing levels of reactive oxygen species (ROS) thereby activating glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which stimulates glycolysis and ATP production, resulting in cell death.

D. DHA is endocytosed into these cells after binding EGF receptors. DHA depletes cytosolic reduced glutathione (GSH) thereby increasing levels of reactive oxygen species (ROS) which inhibits glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which in turn inhibits glycolysis and ATP production and results in cell death.

E. DHA is transported into the cells by overexpressed GLUT1 transporters. DHA depletes cytosolic reduced glutathione (GSH) generating reactive oxygen species (ROS) that inhibit the activities of both RasD and RafV600E resulting in cell death.

Explanation / Answer

The answer is

B. DHA is selectively transported into these cells by overexpressed GLUT1 transporters. DHA depletes cytosolic reduced glutathione (GSH) generating reactive oxygen species (ROS) that inhibit glyceraldehyde 3-phosphate dehydrogenase (GAPDH), thereby inhibiting glycolysis and ATP production and resulting in cell death.

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