L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia Cells

Frontiers in Oncology
Radhakrishnan Chandraprabha VineethaRaveendran Harikumaran Nair

Abstract

Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (As2O3) treatment, which may be possible through the use of dietary supplements in combination. The present investigation evaluates the synergistic mechanism of action of vitamins, such as L-ascorbic acid (L-AA) and α-tocopherol (α-TOC) in As2O3 chemotherapy using human leukemia (HL-60) cells. In vitro assays on the cytotoxicity of As2O3 and vitamins and cellular apoptotic evidences were done; a proteomic investigation with mass spectrometry was also performed. The combination of L-AA and α-TOC potentiates As2O3 cytotoxicity in HL-60 cells, substantiated by depletion in antioxidant status, mitochondrial transmembrane potential, and inhibition of nuclear factor erythroid 2-related factor 2 and B-cell lymphoma 2 transcription factors. Mass spectrometry results showed decreased expression of proteins regulating cell cycle and translation in cells treated with As2O3, L-AA, and α-TOC when compared with As2O3-treated sample. In addition, this combination treatment identified numerous proteins associated with apoptosis and cell stress. HL-60 cells became more prone to As2O3 on exposure to L-AA and α-TOC, indicating that this combination may be a ...Continue Reading

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Citations

Dec 20, 2020·Journal of Food Biochemistry·Adriana Slavova-KazakovaGiovanna Delogu

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Datasets Mentioned

BETA
PXD016771

Methods Mentioned

BETA
electrophoresing
PCR

Software Mentioned

SPSS
Bio
Progenesis
MassLynx4
Quantity One®1 - D Image
rad Image Analysis

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