The majority of breast tumors found by mammograms are benign, and most women who are diagnosed early can be cured of breast cancer. But if allowed to develop, breast cancer can become invasive and metastasize to other parts of the body.
Scientists at the La Jolla, CA, Scripps Research Institute have developed a new therapy that halted the spread of breast cancer and prolonged life in mice.
The team investigated a specific protein complex, called mitochondrial complex I, which controls the energy output of cellular respiration and is the most common site for mitochondrial abnormalities. Previous research suggests that mutations affecting mitochondria--the cell's powerhouse--strongly influence whether a tumor becomes aggressive.
The researchers found that in aggressive breast cancer cells, the balance of important metabolic cofactors processed by complex I--in particular, nicotinamide adenine dinucleotide (NAD+) and NADH, the form it takes after accepting a key electron in the energy production cycle--was disrupted. This NAD+/NADH ratio is an important component of what's known as the redox state of a cell, a measurement that reflects both the metabolic activities and the health of cells.
To test whether this ratio also impacts tumor cell growth, the researchers injected a yeast gene into the breast cancer cells, which shifted the balance toward more NAD+, in turn making the tumor cells less aggressive. The team also noted that higher NADH levels contributed to more aggressive tumors. The researchers then gave mice with breast tumors a mixture of water and nicotinamide, a precursor for NAD+ production, and found that the compound dramatically slowed cancer development and the mice lived longer. The study was published Feb. 15 in The Journal of Clinical Investigation.
The Scripps researchers hope to quickly advance their compound to human trials. NAD+ precursors are already used to treat other conditions, such as for controlling cholesterol levels, so this could help hasten the timeline for testing nicotinamide or other NAD+ precursors in human clinical trials.
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