Isofraxidin enhances hyperthermiainduced apoptosis via redox modification in acute monocytic leukemia U937 cells.
Mol Med Rep
; 27(2)2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-36601752
ABSTRACT
The cellkilling potential of most chemotherapeutic agents is enhanced by a temperature elevation. Isofraxidin (IF) is a coumarin compound widely found in plants, such as the Umbelliferae or Chloranthaceae families. IF induces anticancer effects in lung and colorectal cancer. To the best of our knowledge, the combined effects of hyperthermia (HT) and IF on heatinduced apoptosis have not been reported. Acute monocytic leukemia U937 cells were exposed to HT with or without IF pretreatment. Apoptosis was measured by Annexin VFITC/PI double staining assay using flow cytometry and cell viability was observed by cell counting kit assay, DNA fragmentation. The mechanism involved in the combination was explored by measuring changes in the mitochondrial membrane potential, (MMP), intracellular ROS generation, expression of apoptosis related protein, and intracellular calcium ion level. It was demonstrated that IF enhanced HTinduced apoptosis in U937 cells. The results demonstrated that combined treatment enhanced mitochondrial membrane potential loss and transient superoxide generation increased protein expression levels of caspase3, caspase8 and phosphorylatedJNK and intracellular calcium levels. Moreover, the role of caspases and JNK was confirmed using a pan caspase inhibitor (zVADFMK) and JNK inhibitor (SP600125) in U937 cells. Collectively, the data demonstrated that IF enhanced HTinduced apoptosis via a reactive oxygen species mediated mitochondria/caspasedependent pathway in U937 cells.
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Base de dados:
MEDLINE
Assunto principal:
Leucemia Monocítica Aguda
/
Hipertermia Induzida
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article