Chemoprevention of Lung Carcinogenesis by Dietary Nicotinamide and Inhaled Budesonide.

Arthur R Galbraith,Beverly R Wuertz,Vernon E Steele,Donna E Seabloom,Lee W Wattenberg,Frank G Ondrey,Jennifer D Antonides

doi:10.1158/1940-6207.capr-17-0402

Arthur R Galbraith, Beverly R Wuertz + Show 5 more

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https://doi.org/10.1158/1940-6207.capr-17-0402

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Abstract

Nicotinamide, the amide form of vitamin B3, and budesonide, a synthetic glucocorticoid used in the treatment of asthma, were evaluated to determine their individual and combinational chemopreventive efficacy on benzo(a)pyrene-induced lung tumors in female A/J mice. Nicotinamide fed at a dietary concentration of 0.75% significantly inhibited tumor multiplicity. Nicotinamide by aerosol inhalation at doses up to 15 mg/kg/day did not result in a statistically significant reduction in tumor multiplicity. Finally, dietary nicotinamide was administered with aerosol budesonide and tumor multiplicity reduced by 90% at 1 week and 49% at 8 weeks post last carcinogen dose. We conclude nicotinamide is an effective and safe agent for lung cancer dietary prevention at both early- and late-stage carcinogenesis and that efficacy is increased with aerosol budesonide. Combination chemoprevention with these agents is a well-tolerated and effective strategy which could be clinically advanced to human studies.

Highlights

The leading cause of human cancer mortality in the United States is lung cancer, with an estimated 155,870 deaths in 2017 [1]
For 0.25% dietary nicotinamide, adenoma inhibition ranged from 13% to 46% in the two experiments we performed
We found a dose-dependent decrease in pulmonary adenoma formation with both concentrations, and even discovered nicotinamide was effective at late-stage carcinogenesis prevention

Summary

Introduction

The leading cause of human cancer mortality in the United States is lung cancer, with an estimated 155,870 deaths in 2017 [1]. In spite of continued improvements in surgical, radiation, and chemotherapeutic strategies, more than 70% of all patients with lung cancer still die from this disease [1]. One of the major problems in reducing lung cancer deaths is that carcinogen-induced genotoxic damage and initiation have already taken place long before symptoms of cancer appear. With the recognition that defined steps in the carcinogenesis process exist [2,3,4,5,6], it was realized a number of chemopreventive strategies could be employed, especially suppressive or post carcinogen interventions [7,8,9,10].

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