The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling.

Autor: Liu W; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan., Wu CY; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan., Lu MJ; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan., Chuang YJ; Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan., Tsai EM; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan., Leu S; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan., Lin IL; Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan., Ko CJ; Department of General Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.; School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan., Chiu CC; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan., Chang WT; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan.; Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.; Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Jazyk: angličtina
Zdroj: Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2020 Jan 07; Vol. 2020, pp. 5167292. Date of Electronic Publication: 2020 Jan 07 (Print Publication: 2020).
DOI: 10.1155/2020/5167292
Abstrakt: Lung cancer is a leading cause of cancer death worldwide, and non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer, which is highly metastatic, leading to the poor survival rate of patients. We recently reported that 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), a phenoxyphenol, exerts antihepatoma effects by inducing apoptosis and autophagy. In this study, we further examined the effect of 4-HPPP and its analogs on NSCLC cells. Colony formation assays showed that 4-HPPP exerts selective cytotoxicity against NSCLC H1299 cells; furthermore, the inhibitory effect of 4-HPPP on the proliferation and migration of NSCLC cells was validated using an in vivo zebrafish-based tumor xenograft assay. The flow cytometry-based dichlorofluorescein diacetate (DCF-DA) assays indicated that 4-HPPP caused an increase in reactive oxygen species (ROS) in NSCLC cells, and Western blot assays showed that the major ROS scavenging enzymes superoxide dismutases- (SODs-) 1/2 were upregulated, whereas peroxidase (PRX) was downregulated. Furthermore, 4-HPPP caused both aneuploidization and the accumulation of γ H2AX, a sensor of DNA damage, as well as the activation of double-strand break (DSB) markers, especially Ataxia-telangiectasia-mutated and Rad3-related (ATR) in NSCLC cells. Our present work suggests that the antiproliferative effects of 4-HPPP on lung cancer cells could be due to its phenoxyphenol structure, and 4-HPPP could be a candidate molecule for treating NSCLC by modulating ROS levels and lowering the threshold of polyploidy-specific cell death in the future.
Competing Interests: The authors declare no conflicts of interest.
(Copyright © 2020 Wangta Liu et al.)
Databáze: MEDLINE
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