Protect Healthy Cells from Chemotherapy
Doctors who treat patients with cancer have a balancing act. They give too little chemotherapy and tumors survive, but too much can be life threatening. Now researchers have found that in a series of lab tests, not eating for 48 hours gave healthy cells an edge. University of Southern California Associate Professor of Gerontology and Biological Science Valter Longo says, "The cancer cells have this oncogene, have these mutations that keep them always on. So, they basically are unable to obey the starvation dependent order. Starvation tells [healthy cells] to go into protective mode. The cancer cells, because of their characteristics of not being able to respond to that, just continue on their normal pro-growth track."
Longo notes that, "Virtually all cancer research is focused on...the killing of the cancer cells," but that he wanted instead to see if there was a way to give the healthy cells an edge.
Scientists know from experiments with everything from tiny worms to primates that a lack of food sends cells into a protective mode that can actually extend life. In fact, Longo says his former college advisor helped pioneer this concept of "calorie restriction." Longo describes it as "fasting, not completely, but partially for a long time."
Longo says however, "The cancer cells have these oncogenes, these mutations, that keep them always on (so that they) continue on their pro-growth track" even when the healthy cells have shut down due to a lack of food.
With the healthy cells in protective mode, Longo was able to use more chemotherapy. He wrote in The Proceedings of the National Academy of Sciences he performed several different tests.
One test involved yeast cells that were both subject to starvation and genetically altered to mimic having the starvation condition. They were 1,000 times better protected against cancer-fighting agents.
He also tested normal brain cells and cancerous cells in test tubes and found that the normal cells that were denied normal levels of glucose were protected against several forms of chemotherapy while the cancerous cells were not.
In a third experiment on mice that were starved for 48 hours before chemotherapy, Longo says, "The animals were running around after at least a three-fold higher dose than the maximum...allowed for patients."
However, Longo agrees this research is just the first step, noting that since , "A lot of the cancer patients come in already with weight loss, the starvation is not exactly something that they (doctors) would prefer."
So he is now researching something, "that can do something ... almost as powerful without the starvation." adding that, a drug that mimics the starvation, "would be ideal."
Additionally, he's looking at diet changes short of starvation that might provide the same edge. He notes that, "Just a few changes, very specific changes in the diet and all of a sudden at least the animals in our case are now very resistant again to very high doses of chemo."
Either way, the research on diet is providing new food for thought in our ongoing war against cancer.
This work was published in the Proceedings of the National Academy of Sciences Online Early edition for the week of March 31, 2005 and was funded by a grant from the National Institutes of Health, National Institute on Aging, and a University of Southern California Norris Cancer Center pilot grant.
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