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Inhibiting AKT signaling pathway with cilostazol and meloxicam synergism for suppressing K562 cells in vitro.
Naderbar, Laya; Pazhang, Yaghub; Rezaie, Jafar.
Afiliação
  • Naderbar L; Biology department, Faculty of Sciences, Urmia University, Urmia, Iran.
  • Pazhang Y; Biology department, Faculty of Sciences, Urmia University, Urmia, Iran.
  • Rezaie J; Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
J Biochem Mol Toxicol ; 36(11): e23185, 2022 Nov.
Article em En | MEDLINE | ID: mdl-35920412
ABSTRACT
Despite advances in cancer treatment, chronic myeloid leukemia (CML) is still one of the leading causes of death in the world. Due to the role of inflammation in cancer promotion and progression, thus use of anti-inflammatory agents may suppress cancer cell growth. In this study, we used two anti-inflammatory drugs, cilostazol and meloxicam, for the treatment of CML. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the synergism occurrence was calculated by compusyn software. Annexin V/PI test and Hoechst staining were used to determine the apoptosis rate. To determine the pathway of apoptosis induction, the expression of BCL2 Associated X (Bax) and B-cell lymphoma-2 (Bcl-2) apoptotic genes and caspases activity were evaluated. The cell cycle was analyzed by propidium iodide (PI) staining and flow cytometry. Western blot analysis and immunofluorescence were performed to estimate alterations in Ak strain transforming-1 (AKT-1), phosphprylated AKT-1 (p-AKT-1), adenosine mono-phosphate-kinase (AMPK), and phosphorylated AMPK (p-AMPK) proteins and BCR/ABL and c-Myc distribution, respectively. Results showed that cilostazol, meloxicam, and their combination drug reduced cell viability (p < 0.05). Compared with control, expression of Bax and Bcl-2 decreased in treated cells, respectively (p < 0.05). The caspase-9 activity increased in treated cells compared to control cells (p < 0.001). The applied drugs decreased the protein level of p-AKT-1 while increasing the p-AMPK protein level (p < 0.05). BCR/ABL and c-Myc Protein distribution significantly decreased in treated cells. In conclusion, the combination drug had more cytotoxic effects than cilostazol and meloxicam alone and induced apoptosis by inhibiting AKT-1 activation and c-Myc reduction. Therefore using combination drugs effectively can treat cancers of CML origin.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mielogênica Crônica BCR-ABL Positiva / Proteínas Proto-Oncogênicas c-akt Limite: Humans Idioma: En Revista: J Biochem Mol Toxicol Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / TOXICOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Irã

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mielogênica Crônica BCR-ABL Positiva / Proteínas Proto-Oncogênicas c-akt Limite: Humans Idioma: En Revista: J Biochem Mol Toxicol Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / TOXICOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Irã