Oral Niacin Prevents Photocarcinogenesis and Photoimmunosuppression in Mice

Abstract

Topical nicotinamide (niacinamide) has demonstrable preventive activity against photocarcinogenesis in mice. To better understand how this vitamin prevents ultraviolet (UV) carcinogenesis, we tested systemic administration of another form of the vitamin, niacin, and its capacity to elevate cutaneous nicotinamide-adenine dinucleotide (NAD) content as well as to decrease photoimmunosuppression and photocarcinogenesis. BALB/cAnNTacfBR mice were fed the AIN-76A diet supplemented with 0%, 0.1%, 0.5%, or 1.0% niacin throughout the experiment. UV irradiation consisted of five 30-minute exposures per week to banks of six FS40 Westinghouse sunlamps for 22 weeks in the carcinogenesis experiments, yielding a total cumulative dose of approximately 1.41 x 10(6) Jm-2 of UV-B radiation. Dietary supplementation with 0.1%, 0.5%, or 1.0% niacin reduced the control incidence of skin cancer from 68% to 60%, 48%, and 28%, respectively, at 26.5 weeks after the first UV treatment. Two potential mechanisms by which niacin prevents tumor formation were identified. Photoimmunosuppression, critical for photocarcinogenesis, is measured by a passive transfer assay. Syngeneic, antigenic tumor challenges grew to an average of 91.6 +/- 19.7, 79.8 +/- 11.5, 41.9 +/- 11.7, or 13.2 +/- 4.1 mm2 in naive recipients of splenocytes from UV-irradiated mice treated with 0%, 0.1%, 0.5%, or 1.0% niacin supplementation, respectively, demonstrating niacin prevention of immunosuppression. Niacin supplementation elevated skin NAD content, which is known to modulate the function of DNA strand scission surveillance proteins p53 and poly(ADP-ribose) polymerase, two proteins critical in cellular responses to UV-induced DNA damage. These results clearly demonstrate a dose-dependent preventive effect of oral niacin on photocarcinogenesis and photoimmunosuppression and establish the capacity of oral niacin to elevate skin NAD levels.

NAD+ Modulates p53 DNA Binding Specificity and Function

“…Niacinamide radiosensitizes tumors and prevents UV radiation-induced skin cancer in mice (14,21,22). The data presented here suggest that small molecules that specifically affect p53 protein tetramers can be designed or identified, thus forming a novel basis for the development of molecules that affect p53 function in vivo.…”

Synthesis, physicochemical properties and in vitro cytotoxicity of nicotinic acid ester prodrugs intended for pulmonary delivery using perfluorooctyl bromide as vehicle

“…NAD + + ATP → NADP + + ADP). In fact, nicotinates have been shown to increase NAD levels in cells in culture and in vivo, thus making them chemopreventive agents (Gensler et al, 1999;Jacobson et al, 1995;Jacobson et al, 1999). Therefore the increase of cellular NAD and NADP levels was investigated as an indicator of the successful delivery of nicotinates to the lung following the experimental design used for the determination of the EC20 day 3 .…”

New Dimeric Copper(II) Complex [Cu(5‐MeOsal)2(μ‐nia)(H2O)]2 with Magnetic Exchange Interactions through H‐Bonds

“…Nicotinamide (also known as a niacin derivative or vitamin B 3 ) is a nitrogen donor ligand that has been used in the treatment of various skin diseases (atopic eczema, [1,2] psoriasis and skin cancer [3][4][5] ), and the biological activity of its copper complexes have also been studied. [6] In addition, the biological activity of different salicylic acid derivatives and their copper(II) complexes is well known.…”

“…[7][8][9][10] Meanwhile, salicylatocopper(II) complexes that contain nicotinamide are rarely studied in spite of their possible structural diversities. There are only two examples (out of 26 known structures) [6,11] of polymeric copper(II) complexes where nicotinamide acts as a bridging ligand -[Cu 2 (CH 3 COO) 4 -(µ-nia)] n and {[Cu(sacharinato) 2 (µ-nia)(H 2 O)]·H 2 O} n .…”