Optical Redox Imaging of Treatment Responses to Nampt Inhibition and Combination Therapy in Triple-Negative Breast Cancer Cells

Autor: He N. Xu, Allison Podsednik, Annemarie Jacob, Jinxia Jiang, Lin Z. Li
Jazyk: angličtina
Rok vydání: 2021
Předmět:
NADH and flavoproteins containing FAD
QH301-705.5
Lactate dehydrogenase A
Nicotinamide phosphoribosyltransferase
FX11
Triple Negative Breast Neoplasms
Naphthalenes
Catalysis
Article
Inorganic Chemistry
chemistry.chemical_compound
Piperidines
Antineoplastic Combined Chemotherapy Protocols
Humans
Viability assay
Biology (General)
Physical and Theoretical Chemistry
education
Nicotinamide Phosphoribosyltransferase
redox ratio
FK866/APO866
QD1-999
Molecular Biology
Spectroscopy
chemistry.chemical_classification
Reactive oxygen species
education.field_of_study
Acrylamides
nicotinamide riboside
Chemistry
Cell growth
Organic Chemistry
ROS
General Medicine
Molecular biology
Computer Science Applications
paclitaxel/Taxol
Paclitaxel
Microscopy
Fluorescence
Cell culture
Nicotinamide riboside
Cytokines
Female
Reactive Oxygen Species
Oxidation-Reduction
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 11
International Journal of Molecular Sciences, Vol 22, Iss 5563, p 5563 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22115563
Popis: We evaluated the utility of optical redox imaging (ORI) to identify the therapeutic response of triple-negative breast cancers (TNBC) under various drug treatments. Cultured HCC1806 and MDA-MB-231 cells treated with FK866 (nicotinamide phosphoribosyltransferase (Nampt) inhibitor), FX11 (lactate dehydrogenase A inhibitor), paclitaxel, and their combinations were subjected to ORI, followed by imaging fluorescently labeled reactive oxygen species (ROS). Cell growth inhibition was measured by a cell viability assay. We found that both cell lines experienced significant NADH decrease and redox ratio (Fp/(NADH+Fp)) increase due to FK866 treatment
however, HCC1806 was much more responsive than MDA-MB-231. We further studied HCC1806 with the main findings: (i) nicotinamide riboside (NR) partially restored NADH in FK866-treated cells
(ii) FX11 induced an over 3-fold NADH increase in FK866 or FK866+NR pretreated cells
(iii) FK866 combined with paclitaxel caused synergistic increases in both Fp and the redox ratio
(iv) FK866 sensitized cells to paclitaxel treatments, which agrees with the redox changes detected by ORI
(v) Fp and the redox ratio positively correlated with cell growth inhibition
and (vi) Fp and NADH positively correlated with ROS level. Our study supports the utility of ORI for detecting the treatment responses of TNBC to Nampt inhibition and the sensitization effects on standard chemotherapeutics.
Databáze: OpenAIRE
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