Yuan Liang, Tiehua Zhang, Li Ren
Nov 5, 2020
Citations
1
Influential Citations
23
Citations
Quality indicators
Journal
Environmental toxicology and pharmacology
Abstract
Epidermal growth factor receptor (EGFR) is considered as a valid target in the clinical trials of anticancer therapy and tyrosine kinase inhibitors (TKIs) of EGFR are approved for cancer treatments. In present work, cucurbitacin IIb (CuIIb) was confirmed to exhibit the proliferation inhibitory activity in A549 cells. CuIIb induced apoptosis via STAT3 pathway, which was mitochondria-mediated and caspase-dependent. CuIIb also suppressed the cell cycle and induced G2/M phase cell cycle arrest. CuIIb was capable of suppressing the signal transmitting of the EGFR/mitogen-activated protein kinase (MAPK) pathway which was responsible for the apoptosis and cell cycle arrest. Homogeneous time-resolved fluorescence (HTRF) analysis demonstrated that the kinase activity of EGFR was inhibited by CuIIb. Molecular docking suggested that the CuIIb-EGFR binding fundamentally depends on the contribution of both hydrophobic and hydrogen-bonding interactions. Hence CuIIb may serve as a potential EGFR TKI.