Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung cancer.

ABSTRACT:

Background

Epidermal growth factor receptor (EGFR) activating mutations play crucial roles in the tumorigenesis of human non-small cell lung cancer (NSCLC). The mechanism regarding how EGFR signaling regulates myeloid cell leukemia sequence 1 (Mcl-1) protein stability and ubiquitination remains undefined.

Methods

MTS assay was used for natural product library screening. The effect of formononetin (Formo) on NSCLC cells was determined by MTS assay and soft agar assay. Molecular modeling was performed to analyze the potential different binding modes between Formo and EGFR WT or mutants. Mcl-1 protein level and the inhibitory effect of Formo on EGFR signaling were examined by immunoblot, in vitro kinase assay, in vitro pulldown and ATP competition assays, co-immunoprecipitation

SUBMITTER: Yu X 

PROVIDER: S-EPMC7146989 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature