Laboratory of Tumor Immunology, Medical Biochemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Anticancer Drugs. 2013 Jan;24(1):73-83. doi: 10.1097/CAD.0b013e3283592da8.
LQB 118 is a pterocarpanquinone compound synthesized by our group. It has already been shown that it acts against different leukemia cell lines. However, little is known about the pathway through which this compound induces the death of these cells. In this work, we analyzed the cell death process induced by LQB 118 in K562, a chronic myeloid leukemia cell line, and in Jurkat, a lymphoblastic acute leukemia cell line. For this, we carried out a cell viability assay by MTT, an apoptosis/necrosis assay through the annexin/propidium iodide label, cell cycle by flow cytometry, assessed changes in the mitochondrial membrane potential using DiOC6(3), cytoplasmic calcium analysis by Fluo-3-AM, and a caspase-9 and caspase-12 activity assay. We found that LQB 118 induced apoptosis in both cell lines, measuring caspase-12 and caspase-9 activation, phosphatidylserine externalization, and DNA fragmentation. The compound induced an increase in cytoplasmic calcium on both cell lines. However, the compound could only induce mitochondrial membrane depolarization on K562 cells. Our data show that LQB 118 may have potential therapeutic value for leukemia, being able to overcome multiple resistance mechanisms.
LQB 118 是我们小组合成的紫檀烷醌类化合物。已经证明它可以对抗不同的白血病细胞系。然而，对于这种化合物诱导这些细胞死亡的途径知之甚少。在这项工作中，我们分析了 LQB 118 在慢性髓系白血病细胞系 K562 和淋巴母细胞性急性白血病细胞系 Jurkat 中诱导的细胞死亡过程。为此，我们通过 MTT 进行了细胞活力测定，通过 Annexin/碘化丙啶标记进行了凋亡/坏死测定，通过流式细胞术进行了细胞周期测定，使用 DiOC6(3)评估了线粒体膜电位的变化，通过 Fluo-3-AM 进行了细胞质钙分析，以及进行了 caspase-9 和 caspase-12 活性测定。我们发现 LQB 118 诱导两种细胞系的细胞凋亡，测量 caspase-12 和 caspase-9 的激活、磷脂酰丝氨酸外翻和 DNA 片段化。该化合物在两种细胞系中均诱导细胞质钙增加。然而，该化合物仅能诱导 K562 细胞中线粒体膜去极化。我们的数据表明，LQB 118 可能对白血病具有潜在的治疗价值，能够克服多种耐药机制。
