Kim Seung Hyun, Kim Si-Wouk, Choi Soo Jeong, Kim Yong-Chul, Kim Tae Sung
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Bioorg Med Chem. 2006 Oct 1;14(19):6752-8. doi: 10.1016/j.bmc.2006.05.044. Epub 2006 Jun 12.
The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)2D3 or ATRA and differentiation-enhancing chemicals, adverse effects such as hypercalcemic effects have been ameliorated, and long-term survival has been improved. Indirubin has been demonstrated to exert anti-leukemic effects in cases of chronic myelocytic leukemia. Previously, we synthesized a series of indirubin derivatives and evaluated their anti-proliferative properties against cancer cells. In this study, we determined the enhancing activities of these derivatives on 1,25-(OH)2D3- and ATRA-induced differentiation of human promyelocytic leukemia HL-60 cells. Importantly, some of these derivatives were found to synergistically enhance the differentiation of HL-60 cells in a concentration-dependent manner when coupled with low doses of either 1,25-(OH)2D3 or ATRA. The ability of indirubin derivatives to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA may improve the ultimate outcomes of APL therapy.
诱导分化代表了一种新的且有前景的癌症治疗方法，用1,25 - 二羟基维生素D3 [1,25-(OH)2D3] 或全反式维甲酸（ATRA）治疗急性早幼粒细胞白血病（APL）就很好地说明了这一点。通过使用低浓度、无毒的1,25-(OH)2D3或ATRA与增强分化的化学物质的组合，诸如高钙血症等不良反应已得到改善，长期生存率也有所提高。靛玉红已被证明在慢性粒细胞白血病病例中具有抗白血病作用。此前，我们合成了一系列靛玉红衍生物，并评估了它们对癌细胞的抗增殖特性。在本研究中，我们测定了这些衍生物对1,25-(OH)2D3和ATRA诱导的人早幼粒细胞白血病HL - 60细胞分化的增强活性。重要的是，当与低剂量的1,25-(OH)2D3或ATRA联合使用时，发现其中一些衍生物以浓度依赖的方式协同增强HL - 60细胞的分化。靛玉红衍生物增强1,25-(OH)2D3或ATRA分化潜能的能力可能会改善APL治疗的最终结果。
