Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system
Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system
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DOI：
10.1182/blood.v93.1.268.401a21_268_277
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发表时间：
1999-01-01
期刊：
影响因子：
20.3
通讯作者：
Jing, YK
中科院分区：
文献类型：
--
作者：
Dai, J;Weinberg, RS;Jing, YK
三氧化二砷 (As2O3) 在低浓度（1 至 2 μmol/L）下可诱导急性早幼粒细胞白血病 (APL) 的临床缓解，且 APL 衍生的 NB4 细胞具有最小的毒性和细胞凋亡。我们检查了 NB4 细胞对 As2O3 敏感性的基础，以确定使其他恶性细胞对低浓度 As2O3 产生反应的实验条件。细胞内谷胱甘肽（GSH）含量对As2O3诱导的细胞凋亡具有决定性作用，高敏感NB4细胞的GSH最低，其他细胞系的敏感性与其GSH含量成反比。 t(14;18) B细胞淋巴瘤细胞系的GSH水平较低，对As2O3的敏感性略高于APL细胞。实验上调GSH含量降低了对As2O3的敏感性，抗坏血酸和丁硫氨酸亚砜(BSO)更大程度地降低了GSH，并使恶性细胞对As2O3更敏感。在正常细胞中，抗坏血酸不会增强抗坏血酸诱导的细胞凋亡，这表明抗坏血酸和As2O3的组合可能对某些恶性细胞具有选择性毒性，抗坏血酸在体内增强了As2O3的抗淋巴瘤作用，而没有额外的毒性，因此，单独使用As2O3或与抗坏血酸联合给药可能为淋巴瘤提供一种新的治疗方法。 (C) 1999 年，美国血液学会。
Arsenic trioxide (As2O3) induces clinical remission in acute promyelocytic leukemia (APL) with minimal toxicity and apoptosis in APL-derived NB4 cells at low (1 to 2 mu mol/L) concentration, We examined the basis for NB4 cell sensitivity to As2O3 to identify experimental conditions that would render other malignant cells responsive to low concentrations of As2O3. The intracellular glutathione (GSH) content had a decisive effect on As2O3-induced apoptosis, Highly sensitive NB4 cells had the lowest GSH and the sensitivity of other cell lines was inversely proportional to their GSH content. The t(14;18) B-cell lymphoma cell line had low GSH levels and sensitivity to As2O3 at levels slightly higher than in APL cells, Experimental upmodulation of GSH content decreased the sensitivity to As2O3, Ascorbic acid and buthionine sulfoxide (BSO) decreased GSH to a greater extent, and rendered malignant cells more sensitive to As2O3 As2O3. induced apoptosis was not enhanced by ascorbic acid in normal cells, suggesting that the combination of ascorbic acid and As2O3 may be selectively toxic to some malignant cells, Ascorbic acid enhanced the antilymphoma effect of As2O3 in vivo without additional toxicity, Thus, As2O3 alone or administered with ascorbic acid may provide a novel therapy for lymphoma. (C) 1999 by The American Society of Hematology.