PUBLICATION
The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling
- Authors
- Liu, W., Wu, C.Y., Lu, M.J., Chuang, Y.J., Tsai, E.M., Leu, S., Lin, I.L., Ko, C.J., Chiu, C.C., Chang, W.T.
- ID
- ZDB-PUB-200225-34
- Date
- 2020
- Source
- Oxidative medicine and cellular longevity 2020: 5167292 (Journal)
- Registered Authors
- Chuang, Yung-Jen
- Keywords
- none
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use*
- Apoptosis/drug effects*
- Ataxia Telangiectasia Mutated Proteins/genetics*
- Cell Line, Tumor
- Cell Proliferation/drug effects*
- DNA Repair/drug effects*
- Humans
- Lung Neoplasms/drug therapy*
- Lung Neoplasms/pathology
- Phenols/pharmacology*
- Zebrafish
- PubMed
- 32089770 Full text @ Oxid Med Cell Longev
Citation
Liu, W., Wu, C.Y., Lu, M.J., Chuang, Y.J., Tsai, E.M., Leu, S., Lin, I.L., Ko, C.J., Chiu, C.C., Chang, W.T. (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. 2020:5167292.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping