Santidrian suspected that an imbalance of NAD+ and NADH was responsible for the aggressive behavior in the cancer cells that metastasized. To test this hypothesis, he cleverly transferred a Complex I gene found in yeast to the human breast cancer cells in an attempt boost Complex I activity. He then transplanted the modified cancer cells into mice to see if they would grow and metastasize. He found that the breast cancer cells, which did not have the newly added yeast gene, grew rapidly and metastasized in the mice, while cells that had the working yeast gene did not.
Convinced that the excess NADH was making the tumor cells more aggressive, Santidrian tried a simpler approach. Because NAD+ is made by the cell from vitamin B3, he added a form of vitamin B3 called nicotinamide to the drinking water of the mice. He found that the nicotinamide-supplemented water was able to reduce tumor growth and prevent metastasis, even in the most aggressive breast tumors.
“This is the first study to show a direct relationship between abnormal Complex I and tumor cell aggressiveness,” noted Dr. Felding-Habermann. “It represents the kind of breakthrough discovery we hope to achieve.”
"Complex I is a key component of cellular respiration, the process in which the cell consumes oxygen and produces energy. A major function of Complex I is to generate NAD+, a molecule that is essential for many important processes in a healthy cell. Dr. Santidrian found that the production of NAD+ is disturbed in the aggressive breast cancer cells.
As illustrated here, cellular respiration begins as NADH transfers its energy to Complex I and is converted to NAD+. In healthy cells, there is a balance of NADH and NAD+ levels. In cells with abnormal Complex I function, an excess of NADH accumulates. This causes the tumor cells to panic and activate survival pathways that promote tumor growth."
Dr. Antonio F. Santidrian, is a Senior Research Associate in Felding-Habermann’s lab and is worth a read as well.
Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression
https://www.jci.org/...cles/view/64264
Scripps Research Institute Scientists Find Promising New Approach to Preventing Progression of Breast Cancer
https://www.scripps....215felding.html
https://www.google.c...6011360A1?cl=en
Let's also not forget the ONTRAC study and its contributions.
A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention
Also similar research on liver cancer.
Boosting NAD+ for the prevention and treatment of liver cancer
https://www.ncbi.nlm...les/PMC4905329/