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1.
PLoS One ; 19(5): e0302701, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728286

RESUMO

Although the toxicity of arsenic depends on its chemical forms, few studies have taken into account the ambiguous phenomenon that sodium arsenite (NaAsO2) acts as a potent carcinogen while arsenic trioxide (ATO, As2O3) serves as an effective therapeutic agent in lymphoma, suggesting that NaAsO2 and As2O3 may act via paradoxical ways to either promote or inhibit cancer pathogenesis. Here, we compared the cellular response of the two arsenical compounds, NaAsO2 and As2O3, on the Burkitt lymphoma cell model, the Epstein Barr Virus (EBV)-positive P3HR1 cells. Using flow cytometry and biochemistry analyses, we showed that a NaAsO2 treatment induces P3HR1 cell death, combined with drastic drops in ΔΨm, NAD(P)H and ATP levels. In contrast, As2O3-treated cells resist to cell death, with a moderate reduction of ΔΨm, NAD(P)H and ATP. While both compounds block cells in G2/M and affect their protein carbonylation and lipid peroxidation, As2O3 induces a milder increase in superoxide anions and H2O2 than NaAsO2, associated to a milder inhibition of antioxidant defenses. By electron microscopy, RT-qPCR and image cytometry analyses, we showed that As2O3-treated cells display an overall autophagic response, combined with mitophagy and an unfolded protein response, characteristics that were not observed following a NaAsO2 treatment. As previous works showed that As2O3 reactivates EBV in P3HR1 cells, we treated the EBV- Ramos-1 cells and showed that autophagy was not induced in these EBV- cells upon As2O3 treatment suggesting that the boost of autophagy observed in As2O3-treated P3HR1 cells could be due to the presence of EBV in these cells. Overall, our results suggest that As2O3 is an autophagic inducer which action is enhanced when EBV is present in the cells, in contrast to NaAsO2, which induces cell death. That's why As2O3 is combined with other chemicals, as all-trans retinoic acid, to better target cancer cells in therapeutic treatments.


Assuntos
Trióxido de Arsênio , Arsenicais , Arsenitos , Autofagia , Mitocôndrias , Estresse Oxidativo , Óxidos , Compostos de Sódio , Trióxido de Arsênio/farmacologia , Arsenitos/farmacologia , Arsenitos/toxicidade , Humanos , Estresse Oxidativo/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Compostos de Sódio/farmacologia , Arsenicais/farmacologia , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Óxidos/farmacologia , Morte Celular/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Herpesvirus Humano 4/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Linfoma de Burkitt/virologia , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Linfoma de Burkitt/tratamento farmacológico
2.
Oxid Med Cell Longev ; 2020: 3656419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765806

RESUMO

Curcumin has extensive therapeutic potential because of its antioxidant, anti-inflammatory, and antiproliferative properties. Multiple preclinical studies in vitro and in vivo have proven curcumin to be effective against various cancers. These potent effects are driven by curcumin's ability to induce G2/M cell cycle arrest, induce autophagy, activate apoptosis, disrupt molecular signaling, inhibit invasion and metastasis, and increase the efficacy of current chemotherapeutics. Here, we focus on the hormetic behavior of curcumin. Frequently, low doses of natural chemical products activate an adaptive stress response, whereas high doses activate acute responses like autophagy and cell death. This phenomenon is often referred to as hormesis. Curcumin causes cell death and primarily initiates an autophagic step (mitophagy). At higher doses, cells undergo mitochondrial destabilization due to calcium release from the endoplasmic reticulum, and die. Herein, we address the complex crosstalk that involves mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy, and cell death.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Curcumina/uso terapêutico , Renovação Mitocondrial/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Humanos
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