Chemoprevention of Lung Carcinogenesis by Dietary Nicotinamide and Inhaled Budesonide

Cancer Prev Res (Phila). 2019 Feb;12(2):69-78. doi: 10.1158/1940-6207.CAPR-17-0402. Epub 2019 Jan 3.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Apoptosis
  • Benzo(a)pyrene / toxicity
  • Budesonide / administration & dosage*
  • Carcinogenesis / drug effects*
  • Carcinogenesis / pathology
  • Carcinogens / toxicity
  • Cell Proliferation
  • Dietary Supplements*
  • Female
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Mice
  • Mice, Inbred A
  • Niacinamide / administration & dosage*
  • Tumor Cells, Cultured
  • Vitamin B Complex / administration & dosage

Substances

  • Anti-Inflammatory Agents
  • Carcinogens
  • Vitamin B Complex
  • Niacinamide
  • Benzo(a)pyrene
  • Budesonide