The most aggressive form of liver cancer is called hepato-cellular carcinoma and in 2012 745,000 deaths were attributed to the condition. This cancer has a high mortality rate with few treatment options.
A new study has found that diets rich in nicotinamide ribosome, a derivative of vitamin B3, protects from developing HCC in its initial stages and demonstrates a curative effect of the diet when the cancer was already present. Researchers used a mouse model to reproduce the steps of HCC development from the appearance of the first lesions in the liver to the development of metastasis.
The researchers traced the metabolic pathway leading to the development of cancer and genetically engineered mice that contained high levels of URI only in the liver, in a controlled manner over time. At 30 weeks, the mice with high levels of URI generated sporadic tumours in the liver and even metastasis when the induction lasted longer. The study details how deficiency in nicotinamide adenine dinucleotide (NAD+), a universal compound found in living organisms that is needed to burn calories via cell metabolism, orchestrates the development of the disease.
“An increase in URI reduces cellular NAD+ and as a consequence produces genotoxic stress and DNA damage,” said Nabil Djouder, leader of the study and Head of the Growth Factors, Nutrients and Cancer Group in the BBVA Foundation-CNIO Cancer Cell Biology Programme. “It is still not totally clear, however, why the deficit in NAD+ causes these lesions,” he adds. Supplementation of the diet in genetically modified mice with nicotinamide riboside, a derivative of vitamin B3 that increases intracellular levels of NAD+, negated tumour development. When the same diet was given to mice that had already developed the disease, the size of the tumours was reduced and they eventually disappeared.
The results have been reproduced in other types of cancer such as pancreatic cancer. “We observed the same results in mice with pancreatic adenocarcinoma with regards to DNA damage, so we could conclude that this treatment is effective on tumours caused by oncogene-induced DNA damage and thus, deficit in NAD+,” said Krishna Tummala, first author of the study.
Krishna S. Tummala, Ana L. Gomes, Mahmut Yilmaz, Osvaldo Graña, Latifa Bakiri, Isabel Ruppen, Pilar Ximénez-Embún, Vinayata Sheshappanavar, Manuel Rodriguez- Justo, David G. Pisano, Erwin F. Wagner & Nabil Djouder. Inhibition of De Novo NAD Synthesis by Oncogenic URI Causes Liver Tumorigenesis through DNA Damage. Cancer Cell, November 2014 DOI: 10.1016/j.ccell.2014.10.002