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Bithiophene derivative induced apoptosis and suppression of Akt pathway in mouse leukemic model.
Algharib, Ali Samy; Shanab, Gamila Mohamed-Labib; Abdel-Ghaffar, Abdel-Rahman Badr; Ismail, Mohamed Ahmed; Mohamed, Rania Hassan.
Afiliación
  • Algharib AS; Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
  • Shanab GM; Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
  • Abdel-Ghaffar AB; Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
  • Ismail MA; Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt.
  • Mohamed RH; Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Tumour Biol ; 44(1): 53-67, 2022.
Article en En | MEDLINE | ID: mdl-35431190
BACKGROUND: Bithiophene derivatives show a promising anti-cancer potential. We previously showed that Bithienyl Fluorobenzamidine (BFB) has an anti-proliferative effect against several leukemia cell lines. Acute myeloid leukemia (AML) accounts for 18% of the total leukemia cases worldwide with heavier burden during the past 30 years. Therefore, the main aim remains the discovery of safe and effective medications. OBJECTIVE: The current research aims to investigate the anti-cancer efficacy of BFB and its effect on the apoptosis in the 7,12-Dimethylbenz[a]anthracene (DMBA) induced AML in mice. METHODS: AML was induced in mice by DMBA and then treated by 2 different doses of BFB. After BFB treatment, the hematological and histological pattern changes was examined. Furthermore, the molecular effect of BFB on apoptosis, cell cycle markers and Protein kinase B (Akt) pathway was examined using qPCR, Western blotting and ELISA. RESULTS: BFB treatment ameliorates leukemia histological and hematological markers significantly, despite non-significant changes in normal mice. This improvement exhibits cell cycle arrest and apoptosis induction, represented by elevation of tp53/p53, p21/p21, Caspase3 and downregulation of ckk1/Cdk1 in the bone marrow, as well as Akt pathway suppression. CONCLUSIONS: Our results establishes BFB as a promising therapeutic candidate against AML through cell cycle arrest, apoptosis induction and Akt pathway modulation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Proteínas Proto-Oncogénicas c-akt Límite: Animals / Humans Idioma: En Revista: Tumour Biol Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Proteínas Proto-Oncogénicas c-akt Límite: Animals / Humans Idioma: En Revista: Tumour Biol Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos