Assessment of genotoxic and anti-proliferative effects of doxorubicin in combination with an NF-Kappa B inhibitor in MCF-7 and SKBR-3 cell lines

• Grant number: 13/01596-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2013
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Raquel Alves dos Santos
• Grantee: Natalia dos Santos Gonçalves
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil

Abstract

Nuclear factor-kB ( NF-kB) is a family of highly regulated dimeric transcription factors that activate classical and alternative pathways. Classical is the major one involved, in different cell types, in the response to inflammatory stimuli originated from cytokines such as tumor necrosis factor-a (TNF-a), interleukin 1 (IL-1), and pathogen-associated molecular patterns (PAMPs). The alternative pathway is activated by B-cell activating factor (BAFF), CD40 ligand, and lymphotoxin-B (LT-b). There is yet a third pathway denominated atypical, that is activated in response to genotoxic and replicative stress. Considering the importance of the NF-kB pathway to chemotherapy, once it can be related to mechanisms of resistance in different tumors, some inhibitors for this transcription factor have been synthesized, including the dehydroxylmethylepoxyquinomicin (DHMEQ). Therefore, in the present study, the cellular responses to doxorubicin (a well-known chemotherapic with genotoxic effects)will be evaluated after NF-kB signaling pathway inhibition by DHMEQ using MCF-7n and SKBR-3 breast cancer cell lines. (AU)