Doxorubicin induces apoptosis in Jurkat cells by mitochondria-dependent and mitochondria-independent mechanisms under normoxic and hypoxic conditions

Anti-cancer Drugs
Miguel Mendivil-PerezMarlene Jimenez-Del-Rio

Abstract

In this study, we investigated the molecular mechanism of doxorubicin (dxr)-induced cytotoxicity on Jurkat cells - a model cell of human acute lymphoblastic leukemia - under normoxic (20% O2) and hypoxic (5% O2) conditions. Using in-cell western analysis, immunofluorescence, flow cytometry analysis, and biochemical inhibitors, we evaluated several oxidative stress (OS) and cell death markers. It was found that dxr (5-100 μmol/l) induced apoptosis by OS mechanisms involving DNA fragmentation (8-48%), loss of mitochondrial membrane potential (ΔΨm, 33-92%), and H2O2 production (15-42%) under normoxia. In addition, dxr (10 μmol/l) induced activation and/or nuclei translocation of NF-κB (6.6, 1.6-fold increase), p53 (4.3, 3.1 f), c-Jun (9.5, 5.0 f), apoptosis-inducing factor (AIF) (1.9, 3.9 f), caspase-3 (3.7, 1.9 f), overexpression of Parkin (2.1, 1.2 f)/PINK-1 (2.1 f) proteins, and reduced DJ-1 levels by half compared with untreated cells under normoxia, according to immunofluorescence and in-cell western analysis, respectively. In contrast, dxr (10 μmol/l) could not induce apoptosis in Jurkat cells under hypoxia. Effectively, dxr significantly reduced DNA fragmentation (6%), expression levels of cell death (e.g. p53, c-Jun, caspa...Continue Reading

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Citations

May 20, 2015·International Journal of Molecular Sciences·Zhicheng WangYuan Lu
Jul 3, 2015·Oxidative Medicine and Cellular Longevity·Hasahya TonyZeng Qiutang
Aug 4, 2016·Cell Biology International·Viviana Diaz-AguirreMarlene Jimenez-Del-Rio
Aug 30, 2016·Journal of Natural Products·Valéria GrobárováJan Černý
Jul 7, 2017·Medicinal Research Reviews·Matilde E LleonartAlex Lyakhovich
Apr 11, 2017·Frontiers in Pharmacology·Nikoletta KalenderoglouKaren L Wright
Jun 21, 2020·Cell Biology and Toxicology·Karolina KowalskaAgnieszka Wanda Piastowska-Ciesielska
Oct 25, 2020·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Miguel Mendivil-PerezMarlene Jimenez-Del-Rio

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Methods Mentioned

BETA
flow cytometry
Fluorescence
fluorescence microscopy

Software Mentioned

Windows Multiple Document Interface for flow cytometry
ImageJ
WinMDI
SPSS

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