@article{1e3fa49eda68403ebf2c2a84fdc9d4ee,
title = "HJC0152 suppresses human non–small-cell lung cancer by inhibiting STAT3 and modulating metabolism",
abstract = "Objectives: Signal transducer and activator of transcription 3 (STAT3) is constitutively activated and overexpressed in many cancers, including non–small-cell lung cancer (NSCLC). We recently developed HJC0152 as an orally active STAT3 inhibitor. This study focused on investigating HJC0152's effect and mechanism of action in NSCLC. Materials and methods: We analysed cell proliferation by MTT assays, cell migration by wound healing and transwell assays, protein levels by Western blot, and apoptosis and reactive oxygen species (ROS) level by flow cytometry. A nude mouse tumorigenesis model was established for in vivo experiment. UHPLC-QTOF/MS was used for untargeted metabolomic relative quantitation analysis. Results: We found that HJC0152 exhibited activity against human NSCLC cells in vitro and NSCLC xenograft tumours in vivo via regulating STAT3 signalling and metabolism. HJC0152 efficiently reduced NSCLC cell proliferation, promoted ROS generation, induced apoptosis, triggered DNA damage and reduced motility in A549 and H460 NSCLC cells. Moreover, HJC0152 significantly inhibited the growth of A549 xenograft tumours in vivo. HJC0152 also affected metabolism, significantly decreasing and perturbating levels of several metabolites in the purine, glutathione and pyrimidine metabolism pathways. Conclusions: HJC0152 reduces cellular capacity to scavenge free radicals, leading to ROS generation and accumulation and apoptosis. This study provides a rationale for further developing HJC0152 as a potential therapy for NSCLC and provides insights into the mechanisms by which HJC0152 exerts its anti-cancer effects.",
keywords = "HJC0152, STAT3, lung cancer, metabolism, reactive oxygen species",
author = "Lu Lu and Hang Li and Xin Wu and Jun Rao and Jia Zhou and Saijun Fan and Qiang Shen",
note = "Funding Information: This work was supported by grants from the National Natural Science Foundation of China (Nos. 81703169 to L. Lu, 81572969 and 81730086 to S. Fan), the Technology and Development and Research Projects for Research Institutes, Chinese Ministry of Science and Technology (2014EG150134 to S. Fan), the Tianjin Science and Technology Support Plan Project (14ZCZDSY00001 to S. Fan), the Non‐profit Central Research Institute Fund of Chinese Academy of Medical Sciences (CIFMS, No. 2016‐I2M‐1‐017 and 2017‐I2M‐B&R‐13 to S. Fan), and the Youth Backbone Fund of IRM‐CAMS (Nos. 2019033 to L. Lu). We also thank Amy Ninetto, PhD, ELS, Scientific Publications Services, Research Medical Library, The University of Texas MD Anderson Cancer Center, for her editing of the manuscript. Funding Information: This work was supported by grants from the National Natural Science Foundation of China (Nos. 81703169 to L. Lu, 81572969 and 81730086 to S. Fan), the Technology and Development and Research Projects for Research Institutes, Chinese Ministry of Science and Technology (2014EG150134 to S. Fan), the Tianjin Science and Technology Support Plan Project (14ZCZDSY00001 to S. Fan), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (CIFMS, No. 2016-I2M-1-017 and 2017-I2M-B&R-13 to S. Fan), and the Youth Backbone Fund of IRM-CAMS (Nos. 2019033 to L. Lu). We also thank Amy Ninetto, PhD, ELS, Scientific Publications Services, Research Medical Library, The University of Texas MD Anderson Cancer Center, for her editing of the manuscript. Publisher Copyright: {\textcopyright} 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.",
year = "2020",
month = mar,
day = "1",
doi = "10.1111/cpr.12777",
language = "English (US)",
volume = "53",
journal = "Cell Proliferation",
issn = "0960-7722",
publisher = "Wiley-Blackwell",
number = "3",
}