An article published in the British journal Nature last week reports the anti-cancer activity of the naturally found sugar mannose. Mannose is identical to glucose except for a slight modification on what is known as the #2 carbon of the molecule. The authors go on to state that they found that the level of a certain enzyme called mannose-6-phosphosphate isomerase seems to correlate with the sensitivity of tumors to mannose. The lower the amount of this enzyme the more sensitive the cancers are to mannose. Since this enzyme readily converts mannose to glucose and mannose uses the same transport system as glucose to get into the cell, it appears that when the enzyme is low not enough mannose can be converted to glucose and the cell is effectively starved of its vital energy source. Thus the two-pronged attack of mannose on cancer cells is (1) competing with glucose to get into the cell which reduces glucose levels in the cell ; and (2) in cells with low levels of the converting enzyme, the mannose that gets into the cell cannot be converted to glucose for use as an energy source or as a building block.
Interestingly, the sugar 2-deoxy-D-glucose better known as 2-DG that we and others have been developing as an anti-cancer agent mimics both glucose and mannose based on its unique alteration on the #2 carbon of glucose. The cancer cell cannot figure out whether 2-DG is mimicking glucose or mannose and we have also found that 2-DG kills certain tumor cells most likely by a similar mechanism of starving the cell of glucose. By mimicking both sugars simultaneously, 2-DG has the advantage of both blocking the glucose pathway as well as the mannose pathway and therefore should be effective even in tumors that have high amounts of the enzyme mannose-6-phosphate isomerase.
Overall, this article adds to the overwhelming evidence of the critical role that both mannose and glucose play in the survival of cancer cells and the importance of understanding the mechanisms governing their use for exploiting this universal Achilles heel of cancer: glucose metabolism.
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