Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague 6, Czech Republic; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic.
Physiol Res. 2023 Oct 27;72(S3):S277-S286. doi: 10.33549/physiolres.935184.
Neuroblastoma represents 8-10 % of all malignant tumors in childhood and is responsible for 15 % of cancer deaths in the pediatric population. Aggressive neuroblastomas are often resistant to chemotherapy. Canonically, neuroblastomas can be classified according to the MYCN (N-myc proto-oncogene protein) gene amplification, a common marker of tumor aggressiveness and poor prognosis. It has been found that certain compounds with chelating properties may show anticancer activity, but there is little evidence for the effect of chelators on neuroblastoma. The effect of new chelators characterized by the same functional group, designated as HLZ (1-hydrazino phthalazine), on proliferation (WST-1 and methylene blue assay), cell cycle (flow cytometry), apoptosis (proliferation assay after use of specific pharmacological inhibitors and western blot analysis) and ROS production (fluorometric assay based on dichlorofluorescein diacetate metabolism) was studied in three neuroblastoma cell lines with different levels of MYCN amplification. The molecules were effective only on MYCN-non-amplified cells in which they arrested the cell cycle in the G0/G1 phase. We investigated the mechanism of action and identified the activation of cell signaling that involves protein kinase C.
神经母细胞瘤占儿童期所有恶性肿瘤的 8-10%，占儿科人群癌症死亡人数的 15%。侵袭性神经母细胞瘤通常对化疗有抗性。经典地，神经母细胞瘤可以根据 MYCN（N-myc 原癌基因蛋白）基因扩增进行分类，这是肿瘤侵袭性和预后不良的常见标志物。已经发现，某些具有螯合特性的化合物可能具有抗癌活性，但螯合剂对神经母细胞瘤的作用证据很少。用相同功能基团标记的新型螯合剂 HLZ（1-酰肼邻苯二嗪）对三种 MYCN 扩增程度不同的神经母细胞瘤细胞系的增殖（WST-1 和亚甲基蓝测定法）、细胞周期（流式细胞术）、凋亡（使用特定的药理抑制剂和 Western blot 分析后增殖测定法）和 ROS 产生（基于二氯荧光素二乙酸盐代谢的荧光测定法）的影响进行了研究。这些分子仅对 MYCN 非扩增细胞有效，它们使细胞周期在 G0/G1 期停滞。我们研究了作用机制，并确定了涉及蛋白激酶 C 的细胞信号转导的激活。
