Molecular events and cytotoxic effects of a novel thiosemicarbazone derivative in human leukemia and lymphoma cell lines
| Autor: | Laura Otto Walter, Iris Mattos Santos-Pirath, Ricardo José Nunes, Maria Cláudia Santos-Silva, Mariana Franzoni Maioral, Larissa Sens, Lucas Antonio Pacheco |
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| Rok vydání: | 2018 |
| Předmět: |
MAPK/ERK pathway
Thiosemicarbazones Lymphoma MAP Kinase Signaling System Cytotoxicity Apoptosis Antineoplastic Agents Jurkat cells lcsh:RC254-282 Anticancer activity Lymphoid neoplasms 03 medical and health sciences Jurkat Cells 0302 clinical medicine Cytotoxic T cell Medicine Humans Viability assay Thiosemicarbazone derivative Protein kinase B PI3K/AKT/mTOR pathway Leukemia Cell Death business.industry lcsh:RC633-647.5 Cytotoxins Hematology General Medicine lcsh:Diseases of the blood and blood-forming organs Cell cycle lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Neoplasm Proteins Oncology Cell culture 030220 oncology & carcinogenesis Cancer research business K562 Cells 030215 immunology |
| Zdroj: | Hematology/Oncology and Stem Cell Therapy, Vol 14, Iss 1, Pp 51-64 (2021) |
| ISSN: | 2589-0646 |
| Popis: | The present study aimed to investigate the cytotoxic effect of 38 new thiosemicarbazone derivatives on hematological neoplastic cells lines and to select the most effective compounds to investigate the main molecular mechanisms involved in cell death. Cytotoxicity screening on Daudi and Jurkat cells revealed that only compound 1b met the selection criteria; therefore, it was chosen for further investigation. Cell viability of Daudi, Jurkat, Molt-4, Namalwa, K562, and MM.1S cell lines decreased in a concentration- and time-dependent manner after compound 1b incubation; nevertheless the compound neither caused significant hemolysis nor reduction in peripheral blood mononuclear cell viability. Although no changes were observed on cell cycle or Ki-67 expression, compound 1b induced apoptotic-like cell death with mitochondrial involvement, Bax/Bcl-2 inversion, AIF release, survivin inhibition, and caspase-3 activation in both Daudi and Jurkat cells. Furthermore, the compound reduced NFκB expression in Jurkat cells. In Daudi cells, compound 1b also decreased CHOP, Akt, pAkt, and MAPK/ERK2 expression, thereby suggesting modulation of UPR, PI3K/Akt/mTOR, and MAPK/ERK signaling pathways. Finally, the compound was able to reduce the cell viability of samples collected from patients with different lymphoid neoplasms subtypes, showing that thiosemicarbazones derivatives could be used in the development of new drugs with anticancer activity. |
| Databáze: | OpenAIRE |
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