髓系白血病和淋巴瘤是最常见且经过充分研究的血液恶性肿瘤之一。然而，由于某些亚型的侵袭性和快速进展，治疗这些疾病仍然是一个挑战。考虑到二乙基二硫代氨基甲酸盐在临床前和临床肿瘤学试验中的良好结果，本研究旨在研究二乙基二硫代氨基甲酸钠三水合物（DETC）作为开发治疗血液恶性肿瘤新药原型的潜力。使用 SwissADME 进行计算机分析，以评估 DETC 的理化特性和药代动力学特性。利用 MTT 测定进行的体外研究评估了 DETC 对肿瘤和非肿瘤细胞系的细胞毒性作用。使用选择性指数和溶血测定来确定选择性，同时通过流式细胞术分析促凋亡和抗凋亡蛋白水平来检查肿瘤细胞系的细胞死亡机制。结果表明DETC的理化特性适合口服给药。此外，该化合物对人髓性白血病 (K562) 和伯基特淋巴瘤 (Daudi) 细胞系表现出良好的细胞毒活性，对骨髓微环境中的肿瘤细胞（HS-5 细胞系）的非肿瘤细胞具有高选择性。此外，仅在非常高的浓度下才观察到溶血。 DETC 针对两种肿瘤细胞系的细胞毒性机制涉及细胞周期停滞和活性氧的产生。在 K562 细胞中，细胞死亡是通过细胞凋亡诱导的。需要进行额外的实验来确认 Daudi Burkitt 淋巴瘤细胞中细胞死亡的确切机制。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

Myeloid leukemias and lymphomas are among the most common and well-studied hematological malignancies. However, due to the aggressiveness and rapid progression of certain subtypes, treating these diseases remains a challenge. Considering the promising results of diethyldithiocarbamates in preclinical and clinical oncology trials, this study aimed to investigate the potential of sodium diethyldithiocarbamate trihydrate (DETC) as a prototype for developing new drugs to treat hematological malignancies. In silico analysis using SwissADME was conducted to evaluate the physicochemical characteristics and pharmacokinetic properties of DETC. An in vitro investigation utilizing the MTT assay assessed the cytotoxic effects of DETC on neoplastic and non-neoplastic cell lines. Selectivity was determined using a selectivity index and a hemolysis assay, while the mechanism of cell death in neoplastic cell lines was examined through flow cytometry analysis of pro-apoptotic and anti-apoptotic protein levels. The results demonstrated that the physicochemical characteristics of DETC are suitable for oral administration. Furthermore, the compound showed promising cytotoxic activity against human myeloid leukemia (K562) and Burkitt's lymphoma (Daudi) cell lines, with high selectivity for neoplastic cells over non-neoplastic cells of the bone marrow microenvironment (HS-5 cell line). Moreover, hemolysis was observed only at very high concentrations. The cytotoxicity mechanism of DETC against both neoplastic cell lines involved cell cycle arrest and the production of reactive oxygen species. In K562 cells, cell death was induced via apoptosis. Additional experiments are needed to confirm the exact mechanism of cell death in Daudi Burkitt's lymphoma cells.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.