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The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling
Joint Authors
Tsai, Eing-Mei
Chiu, Chien-Chih
Wu, Chang-Yi
Liu, Wangta
Lu, Mei-Jei
Leu, Steve
Lin, I-Ling
Ko, Chih-Jan
Chang, W. C.
Chuang, Yung-Jen
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-01-08
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
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 γH2AX, 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.
American Psychological Association (APA)
Liu, Wangta& Wu, Chang-Yi& Lu, Mei-Jei& Chuang, Yung-Jen& Tsai, Eing-Mei& Leu, Steve…[et al.]. 2020. The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1204755
Modern Language Association (MLA)
Liu, Wangta…[et al.]. The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1204755
American Medical Association (AMA)
Liu, Wangta& Wu, Chang-Yi& Lu, Mei-Jei& Chuang, Yung-Jen& Tsai, Eing-Mei& Leu, Steve…[et al.]. The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1204755
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204755