Will α-Ketoglutarate Supplementation Pave a New Way for Colorectal Cancer Treatment?
COLORECTAL CANCER predominantly stems from a genetic mutation of APC. In general, a major proportion of people with the mutation will develop polyps; however, only some of the polyps will become cancerous, a poorly understood phenomenon requiring further investigation. In a recent study, researchers discovered that the modification of a natural substance could improve colorectal cancer treatment.
Researchers at the University of California Irvine, Irvine, California, USA, investigated non-genetic factors which drive colorectal cancer. The research centred on the role of the amino acid glutamine in tumour development and a potential method for reversing oncogenesis. Prof Mei Kong form the University of California stated that: “Cancer cells consume a great amount of glutamine to proliferate. But we found that depriving them of glutamine doesn’t kill all the tumour cells.” He further noted that some cells adapt and when deprived of glutamine turn into a more invasive form of cancer.
The study indicated that decreasing intracellular levels of the metabolite α-ketoglutarate after glutamine starvation accompanied the transition from benign to cancerous cells. This discovery propelled further research into the metabolite’s role. A modified version of α-ketoglutarate was administered to animal models with APC mutations and showed that only 23% of those administered the metabolite developed rectal bleeding, a sign of intestinal bleeding, compared to 90% of those that did not receive supplementation. Furthermore, α-ketoglutarate supplementation restrained oncogenesis and protected against disease-associated conditions such as weight loss.
Dr Thai Q. Tran, the paper’s first author, noted: “Supplementation of the modified α-ketoglutarate inhibits a key cancer-development signalling pathway in colon cancer cells, turning them into more normal cells.” Another feat of the study was in how α-ketoglutarate was administered by mixing it into drinking water, making it easier to take and not impacting overall health. Prof Kong proclaimed: “We believe this new knowledge shows great potential for using less-toxic and natural approaches in combination with current therapies to more successfully treat colon cancer while better protecting patients’ overall wellbeing.” The team’s future studies will investigate further modification of the metabolite to specifically target colorectal cancer cells.