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Leuk Res. 2010 Jul;34(7):925-31. doi: 10.1016/j.leukres.2010.01.020. Epub 2010 Feb 19.

Arsenic trioxide and ascorbic acid demonstrate promising activity against primary human CLL cells in vitro.

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1
Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.

Abstract

The compromised antioxidant defense system in chronic lymphocytic leukemia (CLL) suggested a potential use for reactive oxygen species (ROS) generating arsenic trioxide (ATO) and ascorbic acid. While both ATO and ascorbic acid mediate cytotoxicity in CLL B cells as single agents, the efficacy of ATO is enhanced by ascorbic acid. This effect is dependent on increased ROS accumulation, as pretreatment of B-CLL cells with a glutathione reducing buthionine sulfoximine or catalase inhibiting aminotriazole, enhanced ATO/ascorbic acid-mediated cytotoxicity. Pretreatment with reducing agents such as catalase, or thiol antioxidant, N-acetyl cysteine or GSH also abrogated ATO/ascorbic acid-mediated cytotoxicity. Furthermore, Hu1D10-mediated cell death was enhanced with ATO and ascorbic acid, thus justifying potential combination of ATO/arsenic trioxide therapy with antibodies such as Hu1D10 that also cause accumulation of ROS.

PMID:
20171736
PMCID:
PMC4164821
DOI:
10.1016/j.leukres.2010.01.020
[Indexed for MEDLINE]
Free PMC Article
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