Modulation of NAD+ intracellular concentration and its effect in the tumorigenesis induced by benzo[a]pyrene in human bronchial epithelial cells

• Grant number: 16/08784-9
• Support type: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): August 01, 2016
• Effective date (End): July 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Ana Paula de Melo Loureiro
• Grantee: Everson Willian Fialho Cordeiro
• Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Important advances in the treatment of cancer may arise from a better understanding of the molecular origins of the disease and changes underlying cell transformation and proliferation of pre-neoplastic cells. Lung cancer is among the commonest types and is often associated with smoking, being responsible for high mortality rates. In studies of our group, benzo[a]pyrene (B[a]P), a carcinogen present in cigarette smoke and widespread in the environment, is used to induce malignant changes in immortalized human bronchial epithelial cells (BEAS-2B). Our previous results showed that B[±]P causes changes in intermediary metabolism, with an initial drop after the first hour of exposure, of NAD+ levels, NADH, NADPH, ATP, ADP, pyruvate and intermediates of the Krebs cycle followed by a significant increase in the levels of these molecules over 7 days of incubation. In addition, changes were observed for 5-mdC levels and 5-hmdC in the DNA of cells, and increased colony growth in soft-agar without increasing the mutation rate at the HPRT gene. Considering the importance of NAD+ and NADH in regulating the activity of different proteins, this project aims to assess if the modulation of the levels of NAD+ in the BEAS-2B cells exposed to low concentrations of B[±]P affects the formation of colonies in semisolid soft agar medium and counteracts the metabolic, epigenetic and expression changes of some genes sensitive to the redox balance NAD+/NADH, besides the expression of proteins involved in the alteration of metabolism in tumor cells. (AU)