Parthenolide and DMAPT induce cell death in primitive CML cells through reactive oxygen species
| Autor: | Antonieta Chávez-González, Hector Torres-Martinez, Monica L. Guzman, Gabriela Flores‐Lopez, Manuel Ayala-Sánchez, Dafne Moreno-Lorenzana, Peter A. Crooks, Hector Mayani, Sócrates Avilés-Vázquez |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Myeloid Cell cycle checkpoint parthenolide Population Apoptosis Cyclin A 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cyclin D1 hemic and lymphatic diseases Cell Line Tumor Leukemia Myelogenous Chronic BCR-ABL Positive medicine Humans Parthenolide education CML Cell Proliferation education.field_of_study Cell growth Chemistry leukaemic stem cell NF-kappa B ROS Cell Biology Cell Cycle Checkpoints Original Articles Gene Expression Regulation Neoplastic Haematopoiesis 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Molecular Medicine Original Article Stem cell Neoplasm Recurrence Local Reactive Oxygen Species Sesquiterpenes Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | Tyrosine kinase inhibitors (TKI) have become a first‐line treatment for chronic myeloid leuakemia (CML). TKIs efficiently target bulk CML cells; however, they are unable to eliminate the leukaemic stem cell (LSC) population that causes resistance and relapse in CML patients. In this study, we assessed the effects of parthenolide (PTL) and dimethyl amino parthenolide (DMAPT), two potent inhibitors of LSCs in acute myeloid leukaemia (AML), on CML bulk and CML primitive (CD34+lin−) cells. We found that both agents induced cell death in CML, while having little effect on the equivalent normal hematopoietic cells. PTL and DMAPT caused an increase in reactive oxygen species (ROS) levels and inhibited NF‐κB activation. PTL and DMAPT inhibited cell proliferation and induced cell cycle arrest in G0 and G2 phases. Furthermore, we found cell cycle inhibition to correlate with down‐regulation of cyclin D1 and cyclin A. In summary, our study shows that PTL and DMAPT have a strong inhibitory effect on CML cells. Given that cell cycle arrest was not dependent on ROS induction, we speculate that this effect could be a direct consequence of NF‐κB inhibition and if this mechanism was to be evaded, PTL and DMAPT induced cell death would be potentiated. |
| Databáze: | OpenAIRE |
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