Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Invest New Drugs. 2011 Dec;29(6):1156-63. doi: 10.1007/s10637-010-9454-y. Epub 2010 Jun 5.
B-cell chronic lymphocytic leukemia (B-CLL) is an abnormal neoplasic proliferation of B cells, which accumulate mainly in the bone marrow and blood preventing both B cells development in the lymph nodes and the ability to fight against infection. The antitumor agents used in chemotherapy are aimed at inducing malignant cell death, thus limiting the growth and spreading of these cells. However, the lack of specificity for tumor cells exhibited by these agents causes undesirable side effects that have led to the investigation of new therapeutic strategies designed to specifically target malignant cells and thus trigger selective cell destruction. Dequalinium (DQA) is an antitumoral agent that selectively accumulates in the mitochondria and has been shown to display anticancer activity in cells from different malignancies. In the present study, the DQA-induced cytotoxicity in B-CLL cells was analyzed by measuring cell viability and cell death, either by necrosis or apoptosis. Our results support the importance of DQA as a selective and potential antileukemic drug with a higher cytotoxic effect on peripheral blood mononuclear cells from B-CLL patients than in those from healthy donors and encourage the performance of further studies in combination with other agents.
B 细胞慢性淋巴细胞白血病(B-CLL)是 B 细胞的异常肿瘤性增殖,主要积聚在骨髓和血液中,阻止 B 细胞在淋巴结中的发育和抗感染能力。化疗中使用的抗肿瘤药物旨在诱导恶性细胞死亡,从而限制这些细胞的生长和扩散。然而,这些药物对肿瘤细胞缺乏特异性,导致了不良的副作用,这促使人们研究新的治疗策略,旨在专门针对恶性细胞,从而引发选择性细胞破坏。地喹氯铵(DQA)是一种抗肿瘤药物,它选择性地积聚在线粒体中,并已显示出在来自不同恶性肿瘤的细胞中具有抗癌活性。在本研究中,通过测量细胞活力和细胞死亡(坏死或凋亡)来分析 DQA 对 B-CLL 细胞的细胞毒性。我们的研究结果支持 DQA 作为一种选择性和潜在的抗白血病药物的重要性,它对 B-CLL 患者的外周血单个核细胞的细胞毒性作用高于对健康供体的细胞毒性作用,并鼓励与其他药物联合进行进一步的研究。