Abstract
Nicotinamide (NAM) is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme of redox reactions for adenosine triphosphate (ATP) production and for other metabolic processes. As NAD+ status is critical in maintaining cellular energy, vitamin B3 deficiency mainly affects tissues that need high cellular energy causing pellagra and skin sun sensitivity. In animal models, NAD+ deficiency leads to UV sensitivity of the skin, impairs DNA damage response, and increases genomic instability and cancer incidence. Furthermore, NAD+ depletion is associated with human skin aging and cancer. NAM prevents the UV-induced ATP depletion boosting cellular energy and enhances DNA repair activity in vitro and in vivo. Moreover, NAM reduces skin cancer incidence and prevents the immune-suppressive effects of UV in mice. Thus, NAM is involved in the maintenance of genomic stability and may have beneficial effects against skin aging changes and tumor development. Clinical studies showed that topical use of NAM reduces cutaneous aging. Furthermore, oral NAM administration reduces the level of UV-mediated immunosuppression and lowers the rate of non-melanoma skin cancers in high-risk patients. Therefore, NAM replenishment strategy may be a promising approach for skin cancer chemoprevention.
Highlights
Nicotinamide (NAM) is an amide form of vitamin B3, a semi-essential vitamin
NAD+ is required for several cellular processes including adenosine triphosphate (ATP) production, DNA repair and inflammation that are mediated by poly-ADP-ribose polymerase (PARP)-1 and SIRT1 activity
The maintenance of adequate intracellular NAD+ levels and properly SIRT1 and PARP-1 activity is important in preventing DNA damage, genomic instability, and chronic inflammation that seems to be the major contributor to the cancer incidence increase in elderly [17,29,30]
Summary
Nicotinamide (NAM) is an amide form of vitamin B3, a semi-essential vitamin. Many foods, including meat, fish, eggs, legumes, mushrooms, nuts, and grains contain NAM. Persistent DNA damage leads to over-activation of PARP-1 and increased NAD+ catabolism causing suppression of NAD+-dependent ATP generation, energy crisis, and necrotic cell death [22]. PARP-1 and SIRT1 antagonistically interplay regulating energetic homeostasis, genomic integrity and inflammation They share NAD+ and several other substrates, including DNA repair enzymes and NF-kB. NAD+ is required for several cellular processes including ATP production, DNA repair and inflammation that are mediated by PARP-1 and SIRT1 activity. The maintenance of adequate intracellular NAD+ levels and properly SIRT1 and PARP-1 activity is important in preventing DNA damage, genomic instability, and chronic inflammation that seems to be the major contributor to the cancer incidence increase in elderly [17,29,30]
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