title: Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin.
abstract: Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1‑ and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1‑deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wild‑type MDA-MB-231 cells, to demonstrate its effects as a chemo‑ or radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo‑ and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo‑ or radiosensitizing agent regardless of the BRCA1 status in breast cancer.
authors.affiliation: Postgraduate Program on Experimental Biology, Autonomous Metropolitan University at Iztapalapa, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Domínguez-Gómez
authors.affiliation: Unit of Biomedical Research in Cancer, Biomedical Research Institute, National Autonomous University of Mexico/National Cancer Institute, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Chávez
authors.affiliation: Unit of Biomedical Research in Cancer, Biomedical Research Institute, National Autonomous University of Mexico/National Cancer Institute, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Chávez-Blanco
authors.affiliation: Unit of Biomedical Research in Cancer, Biomedical Research Institute, National Autonomous University of Mexico/National Cancer Institute, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Fierro
authors.affiliation: Postgraduate Program on Experimental Biology, Autonomous Metropolitan University at Iztapalapa, Mexico.
authors.forename: J E
authors.initials: JE
authors.lastname: Jiménez-Salazar
authors.affiliation: Department of Reproductive Biology, Autonomous Metropolitan University at Iztapalapa, Mexico.
authors.forename: P
authors.initials: P
authors.lastname: Damián-Matsumura
authors.affiliation: Department of Health Sciences, Autonomous Metropolitan University at Iztapalapa, Mexico.
authors.forename: L E
authors.initials: LE
authors.lastname: Gómez-Quiroz
authors.affiliation: Unit of Biomedical Research in Cancer, Biomedical Research Institute, National Autonomous University of Mexico/National Cancer Institute, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Dueñas-González
mesh_terms: D017209:Apoptosis; D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D061986:MCF-7 Cells; D009536:Niacinamide / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011839:Radiation, Ionizing
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D009536:Niacinamide; D011065:Poly(ADP-ribose) Polymerases; D002945:Cisplatin