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Molecular events and cytotoxic effects of a novel thiosemicarbazone derivative in human leukemia and lymphoma cell lines.
Santos-Pirath, Íris Mattos; Walter, Laura Otto; Maioral, Mariana Franzoni; Pacheco, Lucas Antônio; Sens, Larissa; Nunes, Ricardo José; Santos-Silva, Maria Cláudia.
Afiliación
  • Santos-Pirath ÍM; Experimental Oncology and Hemopathies Laboratory, Clinical Analysis Department, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil; Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil
  • Walter LO; Experimental Oncology and Hemopathies Laboratory, Clinical Analysis Department, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil; Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil
  • Maioral MF; Experimental Oncology and Hemopathies Laboratory, Clinical Analysis Department, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil; Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil
  • Pacheco LA; Structure and Activity Laboratory, Chemistry Department, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil.
  • Sens L; Structure and Activity Laboratory, Chemistry Department, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil; Post-Graduation Program in Chemistry, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil.
  • Nunes RJ; Structure and Activity Laboratory, Chemistry Department, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil; Post-Graduation Program in Chemistry, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil.
  • Santos-Silva MC; Experimental Oncology and Hemopathies Laboratory, Clinical Analysis Department, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil; Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, CEP: 88040-900, Florianópolis, SC, Brazil
Hematol Oncol Stem Cell Ther ; 14(1): 51-64, 2021 Mar.
Article en En | MEDLINE | ID: mdl-32763229
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 compound1b 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, compound1b 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, compound1b 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiosemicarbazonas / Leucemia / Sistema de Señalización de MAP Quinasas / Citotoxinas / Linfoma / Proteínas de Neoplasias / Antineoplásicos Límite: Humans Idioma: En Revista: Hematol Oncol Stem Cell Ther Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Arabia Saudita
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiosemicarbazonas / Leucemia / Sistema de Señalización de MAP Quinasas / Citotoxinas / Linfoma / Proteínas de Neoplasias / Antineoplásicos Límite: Humans Idioma: En Revista: Hematol Oncol Stem Cell Ther Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Arabia Saudita