KCP10043F Represses the Proliferation of Human Non-Small Cell Lung Cancer Cells by Caspase-Mediated Apoptosis via STAT3 Inactivation

Journal of Clinical Medicine
Jeong-Hun LeeKyung-Tae Lee

Abstract

We previously reported that 4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(N,N-dimethylureido)-N'-methylpropylamino]-3,4-dihydroquinazoline (KCP10043F) can induce G1-phase arrest and synergistic cell death in combination with etoposide in lung cancer cells. Here, we investigated the underlying mechanism by which KCP10043F induces cell death in non-small cell lung cancer (NSCLC). Propidium iodide (PI) and annexin V staining revealed that KCP10043F-induced cytotoxicity was caused by apoptosis. KCP10043F induced a series of intracellular events: (1) downregulation of Bcl-2 and Bcl-xL and upregulation of Bax and cleaved Bid; (2) loss of mitochondrial membrane potential; (3) increase of cytochrome c release; (4) cleavage of procaspase-8, procaspase-9, procaspase-3, and poly (ADP-ribose) polymerase (PARP). In addition, KCP10043F exhibited potent inhibitory effects on constitutive or interleukin-6 (IL-6)-induced signal transducer and activator of transcription (STAT3) phosphorylation and STAT3-regulated genes including survivin, Mcl-1, and cyclin D1. Furthermore, STAT3 overexpression attenuated KCP10043F-induced apoptosis and the cleavage of caspase-9, caspase-3, and PARP. Docking analysis disclosed that KCP10043F coul...Continue Reading

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Citations

Jun 18, 2020·Biology·Milad AshrafizadehReza Mohammadinejad
Jul 10, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Zhenzhen GaoYanhong Gu

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Methods Mentioned

BETA
xenografts
enzyme-linked immunosorbent assay
fluorescence-activated cell sorting
Assay
electrophoresis
FACS
Transfection
ELISA
Xenograft
nuclear translocation

Software Mentioned

SwissDock
EADock DSS

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