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Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt.
Otifi, Hassan M; Alshyarba, Mishari; Fayi, Majed Al; Dera, Ayed A; Rajagopalan, Prasanna.
Afiliación
  • Otifi HM; Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Alshyarba M; Department of Surgery, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Fayi MA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
  • Dera AA; Central Research Laboratory, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
  • Rajagopalan P; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
Oncol Res ; 29(3): 217-227, 2021.
Article en En | MEDLINE | ID: mdl-37304673
Targeted therapies are gaining global attention to tackle Renal Cancer (RC). This study aims to screen FPMXY-14 (novel arylidene analogue) for Akt inhibition by computational and in vitro methods. FPMXY-14 was subjected to proton NMR analysis and Mass spectrum analysis. Vero, HEK-293, Caki-1, and A498 cell lines were used. Akt enzyme inhibition was studied with the fluorescent-based kit assay. Modeller 9.19, Schrodinger 2018-1, LigPrep module, and Glide docking were used in computational analysis. The nuclear status was assessed by PI/Hoechst-333258 staining, cell cycle, and apoptosis assays were performed using flow cytometry. Scratch wound and migrations assays were performed. Western blotting was applied to study key signalling proteins. FPMXY-14 selectively inhibited kidney cancer cell proliferation with GI50 values of 77.5 nM and 101.40 nM in Caki-1 cells and A-498 cells, respectively. The compound dose-dependently inhibited Akt enzyme with an IC50 value of 148.5 nM and bound efficiently at the allosteric pocking of the Akt when computationally analyzed. FPMXY-14 caused nuclear condensation/fragmentation, increased the sub G0/G1, G2M populations, and induced early, late phase apoptosis in both cells when compared to controls. Treatment of the compound inhibited wound healing and migration of tumor cells, while proteins like Bcl-2, Bax, and caspase 3 were also altered. FPMXY-14 effectively inhibited the phosphorylation of Akt in these cancer cells, while total Akt was unaltered. FPMXY-14 exhibited anti-proliferative and anti-metastatic activities in kidney cancer cells by attenuating the Akt enzyme. Further pre-clinical research on animals with a detailed pathway elucidation is recommended.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Neoplasias Renales Límite: Animals / Humans Idioma: En Revista: Oncol Res Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Neoplasias Renales Límite: Animals / Humans Idioma: En Revista: Oncol Res Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Estados Unidos