K562细胞
细胞凋亡
外周血单个核细胞
细胞毒性T细胞
自噬
程序性细胞死亡
DNA断裂
细胞毒性
流式细胞术
细胞培养
生物
碎片(计算)
生长抑制
细胞生物学
白血病
细胞生长
分子生物学
癌症研究
生物化学
免疫学
体外
遗传学
生态学
作者
Jeyce Kelle Ferreira de Andrade,Alexandre José da Silva Góes,Vanessa Xavier Barbosa,Mariza Severina de Lima Silva,Mariana Aragão Matos Donato,Christina Alves Peixoto,Gardênia Carmen Gadelha Militão,Teresinha Gonçalves da Silva
标识
DOI:10.1016/j.cbi.2022.110057
摘要
β-lapachone is a 1,2-naphthoquinone of great therapeutic interest that induces cell death by autophagy and apoptosis in tumor cells due to oxidative stress increasing. However, its high toxicity in healthy tissues limits its clinical use, which stimulates the planning and synthesis of more selective analogs. The aim of this study was to investigate the cytotoxic activity of three thiosemicarbazones derived from β-lapachone (BV2, BV3 and BV5) in leukemia cells. Cytotoxicity tests were performed on tumor cells (HL-60, K562, K562-Lucena and MOLT-4) and normal peripheral blood mononuclear cells (PBMCs). Subsequently, the mode of action of compounds was accessed by optical microscopy, transmission electron microscopy or fluorescence microscopy. Flow cytometry analysis was performed to investigate apoptosis induction, cell cycle, DNA fragmentation and mitochondrial depolarization. All derivatives inhibited tumor cell growth after 72 h (IC50 < 10 μM to all cell lines, including the resistant K562-Lucena) with less toxic effects in PBMC cells, being BV3 the most selective compound with selective index (SI) of 275 for HL-60; SI of 40 to K562; SI of 10 for MOLT-4 and SI of 50 to K562-Lucena compared to β-lapachone with SI of 18 to HL-60, SI of 3.7 to K562; SI of 2.4 to MOLT-4 and SI of 0.9 to K562-Lucena. In addition, the K562 or MOLT-4 cells treated with BV3 showed characteristics of both apoptosis and autophagy cell death, mainly by autophagy. These results demonstrate the potent cytotoxic effect of thiosemicarbazones derived from β-lapachone as promising anticancer drugs candidates, encouraging the continuity of in vivo tests.
科研通智能强力驱动
Strongly Powered by AbleSci AI