Is a potential geroprotector a potential carcinogen?
Researchers at the University of Washington, working under the leadership of Dr. Albert H. Kim, have demonstrated that the metabolic signaling pathway associated with aging also contributes to the development of brain cancer.
In the image, cancer stem cells in a slice of the mouse brain emit a green fluorescent glow, which allows researchers to study the effect of inhibition of the signaling mechanism on the ability of cancer stem cells to survive and proliferate.
Earlier studies have demonstrated that an important metabolic cascade known as the NAD+ mediated signaling mechanism is involved in the aging process. Namely, one of its components – nicotinamide mononucleotide (NMN) – reduces the severity of aging in mice. Despite the fact that the safety of this compound for humans is currently being tested in a clinical study conducted in Japan, NMN and other components of the NAD+-mediated signaling pathway are marketed as dietary supplements to slow aging.
However, the new data obtained by the authors demonstrated that patients with glioblastoma die faster with high expression of the NAMPT gene involved in this signaling mechanism on tumor cells. Glioblastoma is the most common and aggressive type of brain cancer, leading to the death of more than 70% of patients within two years after the detection of the disease.
Experiments on human glioblastoma cells have shown that NAMPT promotes the survival and proliferation of cancer stem cells, and its inhibition suppresses the ability of these cells to self-renew.
Similarly, tumors with increased expression of this gene grew very rapidly when implanted in mice and decreased in size under the action of the NAMPT inhibitor.
Moreover, the researchers found that glioblastoma cells reacted to radiotherapy – the standard method of treating this disease – by increasing the expression of genes associated with a NAD+-mediated mechanism, and inhibition of NAMPT before radiotherapy increased their sensitivity to radiation.
All these data suggest that exposure to the NAD+ mediated signaling pathway may improve the treatment outcomes of patients with glioblastoma. However, this may have an impact on other biological mechanisms, including aging.
Many different genes and proteins are involved in this signaling pathway, and its exceptional complexity may be the key to solving specific problems. The authors believe that careful modulation of its various components will allow suppressing cancer growth without accelerating aging and affecting other important biological processes.
They also note that the results obtained are not unequivocal evidence that taking NAD+ precursors accelerates tumor growth, however, they caution that when taking such drugs to slow down aging, it should be remembered that all the risks associated with this have not yet been studied.
Article by Gujar AD et al. An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma is published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from Washington University in St. Louis: Pathway linked to slower aging also fuels brain cancer.
08.12.2016