Evaluation of anticancer effects of 1,2,3-triazoles derivates to the nucleus 1,4-naphthoquinone in human leukemic cell lines.

The triazole nucleus and its derivatives have attracted considerable attention in recent decades for their chemotherapeutic potentials. Specifically, the interest in molecules containing the 1,2,3-triazole as chemotherapeutic agents for various diseases has increased, because they are known to exhibit a wide range of biological activities, such as anti-proliferative and anti-neoplastic. The aim of this study was to evaluate the potencial anti-cancer effect of new triazole derivatives from 1,4-naphthoquinone, elucidating their cytotoxicity and cell death mechanisms involved. From five cancer cell lines tested, leukemic cells (HL-60 and K562) were the most sensitive, and between the eight triazole compounds tested (called C1 to C8), compounds C2 and C3 showed the best IC50 of 14 μM and 41 μM for HL-60 cells and 24 μM and 81 μM for K562 cells, respectively. However, these two compounds showed very little cytotoxic effect towards PBMC normal cells with IC50 superior to 80 μM. Investigating the type of cell death induced by compounds C2 and C3, it was showed that compounds induced apoptosis in HL-60 cells and cell cycle arrest in the S-phase, and necrosis in K562 ones. Cell cycle arrest in S phase was related to the expression of the p21 gene in K562. Results revealed a reduced expression of Bcl-2 protein and an increased expression of BAX protein in HL-60 cells. Moreover, it was found cytochrome c release, suggesting involvement of the intrinsic pathway in apoptosis induction in these cells. Activation of this pathway may be through inhibition of ERK phosphorylation. Our results also showed that pre-treatment of HL-60 cells with N-acetyl cysteine (1 mM) for 1 hour reduced the cytotoxic effect of compounds C2 and C3 for 30,83% and 26,47% respectively; indicating that the induction of apoptosis in HL-60 is mediated by increased production of intracellular ROS. Thus, it can be concluded that C2 and C3 compounds showed cytotoxic effects on HL-60 and K562 cells, so, can be considered as prototype anti-leukemic molecules.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO núcleo triazol e seus derivados têm atraído uma atenção considerável nessas últimas décadas devido ao seu potencial quimioterápico. Mais especificamente, tem se verificado o interesse em moléculas que contêm o grupo 1,2,3-triazol, isto porque esta classe de heterocíclicos é conhecida por exibir uma vasta gama de atividades biológicas, tais como, anti-proliferativo e anti-neoplásico. O objetivo desse trabalho foi o de avaliar o potencial anticancerígeno de novos triazóis derivados do 1,4-naftoquinona, elucidando as suas citotoxicidades e o mecanismo de morte envolvido. Os resultados obtidos revelaram que, das cinco linhagens cancerígenas testadas, as linhagens leucêmicas HL-60 e K562 foram as mais sensíveis, e dentre os oito compostos (denominados C1 a C8) testados, C2 e C3 foram os mais citotóxicos, apresentando CI50 de 14 μM e 41 μM, em HL-60 e de 24 μM e 81 μM em K562, respectivamente. Entretanto, os compostos foram menos citotóxicos nas células normais do sangue periférico humano com CI50 acima 80 μM. Investigando o tipo de morte induzido pelos compostos nas duas linhagens, foi demonstrado que os compostos C2 e C3 induziram apoptose em HL-60. Já nas células K562, este dois derivados provocaram a parada do ciclo celular na fase S e necrose. A parada do ciclo celular na fase S em K562 foi relacionada com a expressão do gene p21. Foi revelado a diminuição da expressão da proteína Bcl-2 e o aumento da expressão da proteína BAX nas células HL-60, e ainda verificou-se a liberação do citocromo c sugerindo a participação da via intrínseca na indução da apoptose em HL-60. A ativação dessa via pode ser via inibição da fosforilação da proteína ERK. Os resultados mostraram também que durante uma hora de pré-tratamento das células HL-60 com o N-acetil cisteina (1 mM), houve a redução da citotoxicidade dos compostos C2 e C3 de 30,83% e 26,47% respectivamente; indicando que a indução da apoptose em HL-60 é mediada pelo aumento da produção das espécies reativas de oxigênio intracelulares. Dessa forma, pode-se concluir que os compostos C2 e C3 apresentaram efeitos citotóxicos frente às linhagens HL-60 e K562, então, podem ser considerados como protótipo de moléculas anti-leucêmicas

The prospect and challenges to the flow of liquid biopsy in Africa

Liquid biopsy technologies have the potential to transform cancer patient management as it others non- invasive diagnosis and real-time monitoring of disease progression and treatment responses. The use of liquid biopsy for non-invasive cancer diagnosis can have pivotal importance for the African continent where access to medical infrastructures is limited, as it eliminates the need for surgical biopsies. To apply liquid biopsy technologies in the African setting, the influence of environmental and population genetic factors must be known. In this review, we discuss the use of circulating tumor cells, cell-free nucleic acids, extracellular vesicles, protein, and other biomolecules in liquid biopsy technology for cancer management with special focus on African studies. We discussed the prospect, barriers, and other aspects that pose challenges to the use of liquid biopsy in the African continent