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

Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (AsO) 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 AsO chemotherapy using human leukemia (HL-60) cells. assays on the cytotoxicity of AsO 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 AsO 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 AsO, L-AA, and α-TOC when compared with AsO-treated sample. In addition, this combination treatment identified numerous proteins associated with apoptosis and cell stress. HL-60 cells became more prone to AsO on exposure to L-AA and α-TOC, indicating that this combination may be a promising approach to increase the outcome of AsO chemotherapy.