Vasconcelos F C, Gattass C R, Rumjanek V M, Maia R C
Laboratório de Hematologia Celular e Molecular, Serviço de Hematologia, Hospital do Câncer I, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil.
Invest New Drugs. 2007 Dec;25(6):525-33. doi: 10.1007/s10637-007-9064-5. Epub 2007 May 23.
Pomolic acid (PA) is a pentacyclic triterpene which has been previously described as active in inhibiting the growth of K562 cell line-originated from chronic myeloid leukemia (CML) in blast crisis-and its vincristine-resistant derivative K562-Lucena1. In this work, cells from CML patients were treated with PA and the apoptotic index was compared with the multidrug resistance (MDR) profile and clinical status of the patients. Our findings show that PA 12.5 microg/ml at 24 h (p = 0.000), at 48 h (p = 0.012) and at 72 h (p = 0.005) has a potent apoptotic index in CML cells as compared to mononuclear cells from healthy donors. PA was capable to induce apoptosis in cells from CML patients exhibiting functional MDR phenotype but not in P-glycoprotein expression. In addition, PA was effective in chronic as well as in blast phase of CML. Moreover, similar apoptotic index induced by PA was observed in low, intermediate and high-risk Sokal score as well as in samples from the group of patients with clinical resistance to interferon and/or imatinib and non-treated patients. These results suggest that PA may be an effective agent for the treatment of CML.
波莫利酸（PA）是一种五环三萜，此前已被描述为对源自慢性粒细胞白血病（CML）急变期的K562细胞系及其长春新碱耐药衍生物K562-Lucena1的生长具有抑制活性。在这项研究中，用PA处理CML患者的细胞，并将凋亡指数与患者的多药耐药（MDR）谱和临床状态进行比较。我们的研究结果表明，与健康供体的单核细胞相比，24小时（p = 0.000）、48小时（p = 0.012）和72小时（p = 0.005）时12.5微克/毫升的PA在CML细胞中具有强大的凋亡指数。PA能够诱导表现出功能性MDR表型的CML患者细胞凋亡，但对P-糖蛋白表达无影响。此外，PA在CML的慢性期和急变期均有效。而且，在低、中、高风险的索卡尔评分患者以及对干扰素和/或伊马替尼临床耐药组患者和未治疗患者的样本中，观察到PA诱导的凋亡指数相似。这些结果表明，PA可能是治疗CML的有效药物。
