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

作者：Biswas Sabyasachi; Zhao Xiaobin; Mone Andrew P; Mo Xiaokui; Vargo Melissa; Jarjoura David; Byrd John C; Muthusamy Natarajan^*

来源：Leukemia Research, 2010, 34(7): 925-931.

DOI：10.1016/j.leukres.2010.01.020

• CLL
• Arsenic trioxide
• Ascorbic acid

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.

• 出版日期2010-7