1. Academic Validation
  2. Kinase inhibitor screening reveals aurora-a kinase is a potential therapeutic and prognostic biomarker of gastric cancer

Kinase inhibitor screening reveals aurora-a kinase is a potential therapeutic and prognostic biomarker of gastric cancer

  • J Cell Biochem. 2021 Oct;122(10):1376-1388. doi: 10.1002/jcb.30015.
Felipe P Mesquita 1 Emerson Lucena da Silva 1 Pedro F N Souza 2 Luina B Lima 1 Jackson L Amaral 2 William Zuercher 3 Louise M Albuquerque 4 Silvia H B Rabenhorst 4 Caroline A Moreira-Nunes 1 Maria E Amaral de Moraes 1 Raquel C Montenegro 1
Affiliations

Affiliations

  • 1 Department of Physiology and Pharmacology, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Brazil.
  • 2 Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
  • 3 Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 4 Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, Brazil.
Abstract

Gastric Cancer is one of the most common and deadly types of Cancer in the world, and poor prognosis with treatment failure is widely reported in the literature. In this context, kinases have been considered a relevant choice for targeted therapy in gastric Cancer. Here, we explore the antiproliferative and antimigratory effects of the AURKA inhibitor and the prognostic and therapeutic value as a biomarker of gastric Cancer. A total of 145 kinase inhibitors were screened to evaluate the cytotoxic or cytostatic effects in the gastric Cancer cell line. Using the Alamar Blue assay, flow cytometry, quantitative polymerase chain reaction, and observation of Caspase 3/7 activity and cell migration, we investigated the antiproliferative, proapoptotic, and antimigratory effects of the AURKA inhibitor. Moreover, AURKA overexpression was evaluated in the gastric cell lines and the gastric tumor tissue. Out of the 145 inhibitors, two presented the highest antiproliferative effect. Both molecules can induce Apoptosis by the caspases 3/7 pathway in addition to inhibiting Cancer cell migration, mainly the AURKA inhibitor. Moreover, molecular docking analysis revealed that GW779439X interacts in the active site of the AURKA Enzyme with similar energy as a well-described inhibitor. Our study identified AURKA overexpression in the gastric Cancer cell line and gastric tumor tissue, revealing that its overexpression in patients with Cancer is correlated with low survival. Therefore, it is feasible to suggest AURKA as a potential marker of gastric Cancer, besides providing robust information for diagnosis and estimated survival of patients. AURKA can be considered a new molecular target used in the prognosis and therapy of gastric Cancer.

Keywords

AURKA; biomarker; gastric cancer; kinase target; prognosis.

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