An Increase in Reactive Oxygen Species by Deregulation of ARNT Enhances Chemotherapeutic Drug-Induced Cancer Cell Death

Shieh, Jiunn Min; Shen, Chi–Yen; Chang, Wei Chiao; Cheng, Hsiu Chi; Chan, Ya Yi; Huang, Wan-Chen; Chang, Wen Chang; Chen, Ben Kuen

doi:10.1371/journal.pone.0099242

Cited by 22 publications

(20 citation statements)

References 34 publications

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“…Under normoxic conditions, ARNT, also known as HIF‐1β, serves as a dimerization partner for several transcription factors, including MDR1, thereby contributing to tumorigenesis and drug resistance . The results of this study show that ARNT expression in CDDP‐resistant GC cells and tissues was higher than that in GC cells and tissues.…”

Section: Discussionmentioning

confidence: 69%

Apoptin‐derived peptide reverses cisplatin resistance in gastric cancer through the PI3K–AKT signaling pathway

et al. 2018

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The prognosis of gastric cancer (GC) remains poor due to clinical drug resistance, and novel drugs are urgently needed. Apoptin‐derived peptide (AdP) is an antitumor polypeptide constructed in our laboratory that has been used to combat cisplatin (CDDP) resistance in GC cells. MTT and colony‐formation assays and Hoechst 33342 staining were used to measure the cytotoxicity of CDDP and AdP in GC cells. Cell apoptosis was measured using an Annexin‐V‐FITC/PI dual staining assay. Western blot analysis was conducted to detect the expression of proteins in the PI3K/AKT signaling pathway and resistance‐related markers. AdP exerted a specific cytotoxic effect on GC cells and CDDP‐resistant GC cells in a concentration‐ and time‐dependent manner. AdP also suppressed cell invasion and migration. Additionally, AdP inhibited the expression of p85, AKT, p‐p85, p‐AKT, multidrug resistance 1 (MDR1), and aryl hydrocarbon nuclear translocator (ARNT) in the PI3K/AKT/ARNT signaling pathway, which promoted apoptosis and necrosis in GC cells. AdP promoted apoptosis in CDDP‐resistant GC cells by suppressing the PI3K/AKT/ARNT signaling pathway and might be considered a candidate agent for the clinical treatment of cisplatin‐resistant GC.

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Section: Discussionmentioning

confidence: 69%

Apoptin‐derived peptide reverses cisplatin resistance in gastric cancer through the PI3K–AKT signaling pathway

et al. 2018

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“…We previously found that 4βHWE selectively killed oral cancer cells but the role of oxidative stress was not addressed. NAC, a free radical scavenger, has been frequently used to investigate the drug‐induced oxidative stress effect . In Figure A, the decrease of cell viability in 4βHWE‐treated oral cancer (Ca9–22) cells were significantly rescued by NAC pretreatment.…”

Section: Resultsmentioning

confidence: 99%

“…NAC, a free radical scavenger, has been frequently used to investigate the drug-induced oxidative stress effect. [29][30][31][32] In Figure 1A, the decrease of cell viability in 4bHWE-treated oral cancer (Ca9-22) cells were significantly rescued by NAC pretreatment. In Figure 1B, the slightly decreased cell viability of 4bHWE-treated oral normal cells (HGF-1) was also rescued with slightly improved proliferation.…”

Section: Assessment Of Cell Viability Of 4bhwe-treated Oral Cancer mentioning

confidence: 96%

4β‐Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells

Tang

Huang

Wang

et al. 2017

Environmental Toxicology

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Reactive oxygen species (ROS) induction had been previously reported in 4β-hydroxywithanolide (4βHWE)-induced selective killing of oral cancer cells, but the mechanism involving ROS and the DNA damage effect remain unclear. This study explores the role of ROS and oxidative DNA damage of 4βHWE in the selective killing of oral cancer cells. Changes in cell viability, morphology, ROS, DNA double strand break (DSB) signaling (γH2AX foci in immunofluorescence and DSB signaling in western blotting), and oxidative DNA damage (8-oxo-2'deoxyguanosine [8-oxodG]) were detected in 4βHWE-treated oral cancer (Ca9-22) and/or normal (HGF-1) cells. 4βHWE decreased cell viability, changed cell morphology and induced ROS generation in oral cancer cells rather than oral normal cells, which were recovered by a free radical scavenger N-acetylcysteine (NAC). For immunofluorescence, 4βHWE also accumulated more of the DSB marker, γH2AX foci, in oral cancer cells than in oral normal cells. For western blotting, DSB signaling proteins such as γH2AX and MRN complex (MRE11, RAD50, and NBS1) were overexpressed in 4βHWE-treated oral cancer cells in different concentrations and treatment time. In the formamidopyrimidine-DNA glycolyase (Fpg)-based comet assay and 8-oxodG-based flow cytometry, the 8-oxodG expressions were higher in 4βHWE-treated oral cancer cells than in oral normal cells. All the 4βHWE-induced DSB and oxidative DNA damage to oral cancer cells were recovered by NAC pretreatment. Taken together, the 4βHWE selectively induced DSB and oxidative DNA damage for the ROS-mediated selective killing of oral cancer cells.

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“…By the addition of ROS scavenger NAC to experiments, the role of EANA‐induced oxidative stress on cell viability was clarified . Figure B shows that NAC pretreatment significantly increases the cell viability of all EANA treatments in oral cancer cells than EANA alone ( P < .05‐.0001), whereas the cell viability of oral normal cells (HGF‐1) maintains healthy regardless of NAC pretreatment.…”

Section: Resultsmentioning

confidence: 99%

Ethyl acetate extract of Nepenthes adrianii x clipeata induces antiproliferation, apoptosis, and DNA damage against oral cancer cells through oxidative stress

Tang

Peng

Cheng

et al. 2019

Environmental Toxicology

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Nepenthes plants are regarded as a kind of Traditional Chinese Medicine for several diseases but its anticancer activity remain unclear. The subject of this study is to evaluate the antiproliferation effects on oral cancer cells by Nepenthes plants using ethyl acetate extract of Nepenthes adrianii x clipeata (EANA). Cell viability was detected using MTS assay. Its detailed mechanisms including cell cycle, apoptosis, oxidative stress, and DNA damage were explored by flow cytometry or western blotting. For 24 hours EANA treatment, five kinds of oral cancer cells (CAL 27, Ca9-22, OECM-1, HSC-3, and SCC9) show IC 50 values of cell viability ranging from 8 to 17 μg/mL but the viability of normal oral cells (HGF-1) remains over 80%. Subsequently, CAL 27 and Ca9-22 cells with high sensitivity to EANA were chosen to investigate the detailed mechanism. EANA displays the time course and concentration effects for inducing apoptosis based on flow cytometry (subG1 and annexin V analyses) and western blotting [cleaved poly (ADP-ribose) polymerase (c-PARP)]. Oxidative stress and DNA damage were induced by EANA treatments in oral cancer cells through reactive oxygen species (ROS),

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An Increase in Reactive Oxygen Species by Deregulation of ARNT Enhances Chemotherapeutic Drug-Induced Cancer Cell Death

Cited by 22 publications

References 34 publications

Apoptin‐derived peptide reverses cisplatin resistance in gastric cancer through the PI3K–AKT signaling pathway

Apoptin‐derived peptide reverses cisplatin resistance in gastric cancer through the PI3K–AKT signaling pathway

4β‐Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells

Ethyl acetate extract of Nepenthes adrianii x clipeata induces antiproliferation, apoptosis, and DNA damage against oral cancer cells through oxidative stress

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