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 Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): August 01, 2016
• Effective date (End): September 30, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Ana Paula de Melo Loureiro
• Grantee: Everson Willian Fialho Cordeiro
• Host 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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CORDEIRO, Everson Willian Fialho. Modulation of intracellular concentration of NAD+ and its effect on benzo[a]pyrene-induced tumorigenesis in human epithelial bronchial cells. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.