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A novel thiosemicarbazone as a promising effective and selective compound for acute leukemia. | LitMetric

AI Article Synopsis

  • Acute leukemias are aggressive cancers that are challenging to treat due to current chemotherapy drugs affecting both cancerous and healthy cells, prompting the need for more targeted therapies.
  • This study investigates a new compound called LAP17, a thiosemicarbazone, which has shown strong cytotoxic effects specifically on acute leukemia cell lines (K562 and Jurkat) by inducing apoptosis through various mechanisms.
  • LAP17 causes cell cycle arrest at the G2/M phase and does not harm non-cancerous cells, indicating its potential as a selective and effective new treatment for leukemia.

Article Abstract

Acute leukemias are a heterogeneous group of aggressive malignant neoplasms associated with severe morbidities due to the nonselectivity of current chemotherapeutic drugs to nonmalignant cells. The investigation of novel natural and synthetic structures that might be used for the development of new drugs with greater efficiency and selectivity to leukemic cells is mandatory. In this context, thiosemicarbazones have been well described in the literature by their several biological properties and their reaction is known as versatile, low-cost, and highly chemoselective. With this perspective, this study aimed to investigate the cytotoxic effect and the main death mechanisms of a novel thiosemicarbazone (LAP17) on acute leukemia cell lines K562 and Jurkat. The results show that the strong cytotoxic effect of LAP17 to leukemic cells is due to apoptosis induction, which resulted in caspase-3 activation and DNA fragmentation. Intrinsic apoptosis seems to be related to the inversion of Bax/Bcl-2 expression, ΔΨm loss, and AIF release, whereas extrinsic apoptosis was initiated by FasR. Gene-expression profiling of HL-60 cells treated with LAP17 by the microarray technique revealed a significant enrichment of gene sets related to cell cycle arrest at G2/M. Accordingly, K562 and Jurkat cells treated with LAP17 revealed a clear arrest at G2/M phase. Taking into consideration that LAP17 was not cytotoxic to nonhematological cells (peripheral blood mononuclear cell and erythrocytes), these results suggest that LAP17 is a promising new compound that might be used as a prototype for the development of new antileukemic agents.

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Source
http://dx.doi.org/10.1097/CAD.0000000000000780DOI Listing

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