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Hsp Inhibitor is Affective Against Adenocarcinomic Human Alveolar Basal Epithelial Cells Through Modulating ERK/MAPK Signaling Pathway. | LitMetric

AI Article Synopsis

  • The ERK-MAPK pathway is crucial for cell growth and survival, and its deregulation, along with abnormal levels of Heat Shock Protein 90 (HSP90), is commonly found in non-small cell lung cancer (NSCLC).
  • This study explores new perimidine-pyrazole compounds that inhibit HSP90's role in cancer cell survival, aiming to block ERK-MAPK pathway deregulation and promote cancer cell death.
  • Results showed that these compounds led to significant cancer-inhibitory effects, promoting cell senescence and apoptosis in NSCLC cells, suggesting they could be developed into new anticancer therapies.

Article Abstract

The extracellular signal-regulated kinase (ERK) - mitogen-activated protein kinase (MAPK) pathway regulates cell proliferation, differentiation, and apoptosis. Heat Shock Protein 90 (HSP90) is required to activate proto-oncogenic protein kinases and promotes tumor growth through anti-apoptotic effects on A549-non-small cell lung cancer (NSCLC). Therefore, deregulation of the ERK-MAPK pathway and abnormal expression of HSP90 are reasonably frequent events in NSCLC. In this study, novel perimidine-pyrazole compounds employed to block ERK-MAPK deregulation through inhibiting HSP dependent cancer cell survival mechanisms. A set of perimidine-pyrazole derivatives effects was monitored on NSCLC cell line. Array experiments performed to understand the effect of the compounds on signaling pathways and results were analyzed by gene enrichment analysis. Further, senescence and apoptosis experiments were performed to support the enrichment results along with in silico methods to determine perimidine-pyrazole/HSP interactions. Treatment of NSCLC cells with perimidine-pyrazole derivatives displayed cancer-inhibitory, pro-senescent and pro-apoptotic effects on NSCLC cells through ERK/MAPK pathway and these compounds are promising templates for designing anticancer drugs.

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Source
http://dx.doi.org/10.1002/cbdv.202301422DOI Listing

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