Anti-cancer Ketone
Ketogenic diet inhibits colorectal cancer in mice
Ekaterina Petrova, PCR.news
Colorectal cancer (CRC) is the third most common form of cancer in the world, more than 880,000 people die from it every year (as of 2018). Among the risk factors for CRC are alcohol and red meat abuse, a diet low in fiber and high in sugar. However, until now it was unclear whether there are diets that restrain or prevent carcinogenesis.
A team of scientists from the USA decided to test how different diets affect the development of colorectal cancer. The study used model mice in which CRC was induced by injection of azoxymethane and sodium dextran sulfate.
Scientists have found that mice on a diet low in carbohydrates and high in fat are very resistant to the development of colorectal tumors. Two ketogenic diets with a 90 percent fat content and a low carbohydrate content (one used pork fat, and the other used Crisco cooking fat, consisting mainly of soy oil) prevented the development of tumors in most mice. When mice with an already developed tumor were transferred to such diets, its growth slowed down.
A more detailed analysis showed that the proliferation of colon epithelial cells decreases against the background of low-carbohydrate diets. High fat intake against the background of a lack of carbohydrates leads to the production of ketone bodies by the liver — acetoacetate and beta-hydroxybutyrate (BHB), which are used by the body as an energy source. Scientists have suggested that it is ketone bodies that slow down the growth of the epithelium and, accordingly, the development of the tumor. Experiments on organoids obtained from mouse intestinal cells have shown that only BHB gives such an effect.
The authors sequenced the RNA of BHB-treated organoids and found that this molecule alters gene expression. It activates the surface receptor Hcar2, which stimulates the expression of the transcription regulator Hopx, and as a result, cell proliferation slows down. In the experiment, this was expressed in the slow growth of organoids.
Experiments with organoids from cells of healthy human intestinal epithelium gave the same result due to a similar molecular mechanism. BHB acted on tumor cells if they expressed the Hcar2 and Hopx genes.
The results of the study may help in the fight against colorectal cancer. There are BHB dietary supplements, however, before recommending them to patients, it is necessary to conduct clinical trials. This is exactly what the authors of the work plan to do.
Article Dmitrieva-Posocco O. et al. β-Hydroxybutyrate suppresses colorectal cancer is published in the journal Nature.
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