Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
Leuk Res. 2010 Jul;34(7):925-31. doi: 10.1016/j.leukres.2010.01.020. Epub 2010 Feb 19.
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.
慢性淋巴细胞白血病 (CLL) 抗氧化防御系统受损，表明活性氧 (ROS) 生成三氧化二砷 (ATO) 和抗坏血酸可能具有潜在用途。虽然 ATO 和抗坏血酸作为单一药物均可介导 CLL B 细胞的细胞毒性，但抗坏血酸可增强 ATO 的功效。这种作用依赖于 ROS 积累的增加，因为用谷胱甘肽还原剂丁硫氨酸亚砜或过氧化氢酶抑制剂氨基三唑预处理 B-CLL 细胞可增强 ATO/抗坏血酸介导的细胞毒性。用过氧化氢酶或硫醇抗氧化剂、N-乙酰半胱氨酸或 GSH 等还原剂预处理也可消除 ATO/抗坏血酸介导的细胞毒性。此外，用 ATO 和抗坏血酸增强了 Hu1D10 介导的细胞死亡，因此有理由将 ATO/三氧化二砷治疗与 Hu1D10 等抗体联合使用，Hu1D10 也会导致 ROS 的积累。
