| Full text | |
| Author(s): |
Vicari, Hugo Passos
;
Gomes, Ralph da Costa
;
Lima, Keli
;
Rossini, Nicolas de Oliveira
;
Rodrigues Junior, Manoel Trindade
;
de Miranda, Livia Bassani Lins
;
Dias, Marcio Vinicius Bertacini
;
Costa-Lotufo, Leticia Veras
;
Coelho, Fernando
;
Machado-Neto, Joao Agostinho
Total Authors: 10
|
| Document type: | Journal article |
| Source: | TOXICOLOGY IN VITRO; v. 99, p. 11-pg., 2024-06-01. |
| Abstract | |
Acute leukemias present therapeutic challenges despite advances in treatments. Microtubule inhibitors have played a pivotal role in cancer therapy, inspiring exploration into novel compounds like C2E1 from the cyclopenta[b]indole class. In the present study, we investigated C2E1's potential as a therapeutic agent for acute leukemia at molecular, cellular, and genetic levels. C2E1 demonstrated tubulin depolarization activity, significantly reducing leukemia cell viability. Its impact involved multifaceted mechanisms: inducing apoptosis, arrest of cell cycle progression, and inhibition of clonogenicity and migration in leukemia cells. At a molecular level, C2E1 triggered DNA damage, antiproliferative, and apoptosis markers and altered gene expression related to cytoskeletal regulation, disrupting essential cellular processes crucial for leukemia cell survival and proliferation. These findings highlight C2E1's promise as a potential candidate for novel anti-cancer therapies. Notably, its distinct mode of action from conventional microtubule-targeting drugs suggests the potential to bypass common resistance mechanisms encountered with existing treatments. In summary, C2E1 emerges as a compelling compound with diverse effects on leukemia cells, showcasing promising antineoplastic properties. Its ability to disrupt critical cellular functions selective to leukemia cells positions it as a candidate for future therapeutic development. (AU) | |
| FAPESP's process: | 19/01700-2 - Functional investigation of Stathmin 1 in proliferation, differentiation and apoptosis in acute promyelocytic leukemia model |
| Grantee: | Hugo Passos Vicari |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 19/23864-7 - Comprehensive analysis of genomic data for identification and validation of novel therapeutic targets involved in cellular cytoskeleton regulation in acute Leukemia |
| Grantee: | João Agostinho Machado Neto |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 21/11606-3 - Investigation of the antineoplastic effects of novel PIP4K2 and HDAC inhibitors in hematologic malignancies |
| Grantee: | João Agostinho Machado Neto |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery |
| Grantee: | Glaucius Oliva |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 21/01460-1 - Investigation of the antineoplastic potential of new drugs that modulate microtubule dynamics in Acute Myeloid Leukemia |
| Grantee: | Hugo Passos Vicari |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |