High intake of dietary glucose could increase the expression of specific genes that promote tumour growth, according to new research in mice.
The study – published in Cell Cycle – raises questions about the consequences of a sugar-rich diet for people with cancer. The research suggests for the first time that dietary intake of glucose could increase the activity of a powerful gene (known as p53) that can lead to increases tumour growth rates.
“We found that a carbohydrate-free dietetic regimen that lowers the fasting glucose levels blunts p53 mutant expression and oncogenic activity relative to a normal diet in several animal model systems,” say the research team.
Led by Dr Maria Laura Avantaggiati from Georgetown Lombardi Comprehensive Cancer Center, USA, the team said that such findings do not, however, suggest that people with cancer should put a ban on sugar just yet.
"We have not studied the effect of glucose on cancer growth in humans, so we cannot make that link at this point," said Avantaggiati.
"Various types of dietetic interventions have been shown to affect cancer growth, but no one had ever shown, before this study, that the amount of carbohydrates could affect the expression of mutant p53," she said. "However, we need to be cautious about translating a finding from mice to humans. Our research into that connection is ongoing."
Cancer and diet
Avantaggiati added that if her team can show that this is a generalized phenomenon, “it could have important implications for care, and may help explain the observation that human diet does affect cancer treatment and growth."
The team noted that while a normal p53 gene acts as a tumour suppressor a mutant version of p53 is commonly found in cancer cells, and many scientists believe that this mutated gene can work to boost the growth of tumours, rather than slow it.
For example, high levels of mutant p53 expression has long been linked to cancer aggressiveness, resistance to therapy, worse outcomes and even relapse after therapy, explain the researchers.
“These findings indicate that the stability of mutant forms of p53 is influenced by the levels of glucose and by dietetic habits,” suggest the researchers.
As part of the five-year study, Avantaggiati and her team sought to understand how to reduce the levels of proteins generated by mutations of the p53 gene in tumours.
Avantaggiati said this is an important issue because not only do the majority of human tumours contain too much mutant p53 protein, but also because researchers now believe that current chemotherapy drugs actually increase the amount of mutant p53 in cancer, leading to possible resistance to drugs.
“Mutant p53 proteins are misfolded, but they are usually not efficiently degraded,” explained Avantaggiati. “However, when autophagy [cell clearing] is induced by glucose restriction, this process eliminates them, and this is what we were hoping to see.”
The researchers conducted a series of studies to see if a link could be established in animal models. These tests suggested that mutant p53 levels were sensitive to glucose restriction, but additional research was needed to determine whether this phenomenon had an impact upon tumour growth.
While a further test found that mice fed the low carbohydrate diet had restricted growth of their tumours, the growth of tumours was blocked – but only when the tumours expressed the mutant p53.
"This series of studies helps establish the mechanisms of why a low carbohydrate diet slows tumour growth," said Avantaggiati.
Source: Cell Cycle
Volume 11, Issue 23 December 1, 2012, doi: 10.4161/cc.22778
“Dietary downregulation of mutant p53 levels via glucose restriction: Mechanisms and implications for tumor therapy”
Authors: Olga Catalina Rodriguez, Sujatra Choudhury, Vamsi Kolukula, Eveline E. Vietsch, et al