scholarly journals Nepenthes Extract Induces Selective Killing, Necrosis, and Apoptosis in Oral Cancer Cells

2021 ◽  
Vol 11 (9) ◽  
pp. 871
Author(s):  
Kun-Han Yang ◽  
Jen-Yang Tang ◽  
Yan-Ning Chen ◽  
Ya-Ting Chuang ◽  
I-Hsuan Tsai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Annexin V ◽  
High Sensitivity ◽  
Heme Oxygenase 1 ◽  
Mitochondrial Membrane Depolarization ◽  
Oral Cancer Cells ◽  
Stress Dependent

Ethyl acetate Nepenthes extract (EANT) from Nepenthes thorellii × (ventricosa × maxima) shows antiproliferation and apoptosis but not necrosis in breast cancer cells, but this has not been investigated in oral cancer cells. In the present study, EANT shows no cytotoxicity to normal oral cells but exhibits selective killing to six oral cancer cell lines. They were suppressed by pretreatment of the antioxidant inhibitor N-acetylcysteine (NAC), demonstrating that EANT-induced cell death was mediated by oxidative stress. Concerning high sensitivity to EANT, Ca9-22 and CAL 27 oral cancer cells were chosen for exploring detailed selective killing mechanisms. EANT triggers a mixture of necrosis and apoptosis as determined by annexin V/7-aminoactinmycin D analysis. Still, they show differential switches from necrosis at a low (10 μg/mL) concentration to apoptosis at high (25 μg/mL) concentration of EANT in oral cancer cells. NAC induces necrosis but suppresses annexin V-detected apoptosis in oral cancer cells. Necrostatin 1 (NEC1), a necroptosis inhibitor, moderately suppresses necrosis but induces apoptosis at 10 μg/mL EANT. In contrast, Z-VAD-FMK, a pancaspase inhibitor, slightly causes necrosis but suppresses apoptosis at 10 μg/mL EANT. Furthermore, the flow cytometry-detected pancaspase activity is dose-responsively increased but is suppressed by NAC and ZVAD, although not for NEC1 in oral cancer cells. EANT causes several oxidative stress events such as reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane depolarization. In response to oxidative stresses, the mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), heme oxygenase 1 (HMOX1), and thioredoxin (TXN), are overexpressed in oral cancer cells. Moreover, EANT also triggers DNA damage, as detected by γH2AX and 8-oxo-2′-deoxyguanosine adducts. The dependence of oxidative stress is validated by the evidence that NAC pretreatment reverts the changes of cellular and mitochondrial stress and DNA damage. Therefore, EANT exhibits antiproliferation involving an oxidative stress-dependent necrosis/apoptosis switch and DNA damage in oral cancer cells.

scholarly journals Manoalide Preferentially Provides Antiproliferation of Oral Cancer Cells by Oxidative Stress-Mediated Apoptosis and DNA Damage

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1303 ◽  
Author(s):  
Hui-Ru Wang ◽  
Jen-Yang Tang ◽  
Yen-Yun Wang ◽  
Ammad Ahmad Farooqi ◽  
Ching-Yu Yen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Annexin V ◽  
Cancer Drug ◽  
Dna Damages ◽  
Atp Production ◽  
Oral Cancer Cells ◽  
Stress Dependent

Marine sponge-derived manoalide has a potent anti-inflammatory effect, but its potential application as an anti-cancer drug has not yet been extensively investigated. The purpose of this study is to evaluate the antiproliferative effects of manoalide on oral cancer cells. MTS assay at 24 h showed that manoalide inhibited the proliferation of six types of oral cancer cell lines (SCC9, HSC3, OC2, OECM-1, Ca9-22, and CAL 27) but did not affect the proliferation of normal oral cell line (human gingival fibroblasts (HGF-1)). Manoalide also inhibits the ATP production from 3D sphere formation of Ca9-22 and CAL 27 cells. Mechanically, manoalide induces subG1 accumulation in oral cancer cells. Manoalide also induces more annexin V expression in oral cancer Ca9-22 and CAL 27 cells than that of HGF-1 cells. Manoalide induces activation of caspase 3 (Cas 3), which is a hallmark of apoptosis in oral cancer cells, Ca9-22 and CAL 27. Inhibitors of Cas 8 and Cas 9 suppress manoalide-induced Cas 3 activation. Manoalide induces higher reactive oxygen species (ROS) productions in Ca9-22 and CAL 27 cells than in HGF-1 cells. This oxidative stress induction by manoalide is further supported by mitochondrial superoxide (MitoSOX) production and mitochondrial membrane potential (MitoMP) destruction in oral cancer cells. Subsequently, manoalide-induced oxidative stress leads to DNA damages, such as γH2AX and 8-oxo-2’-deoxyguanosine (8-oxodG), in oral cancer cells. Effects, such as enhanced antiproliferation, apoptosis, oxidative stress, and DNA damage, in manoalide-treated oral cancer cells were suppressed by inhibitors of oxidative stress or apoptosis, or both, such as N-acetylcysteine (NAC) and Z-VAD-FMK (Z-VAD). Moreover, mitochondria-targeted superoxide inhibitor MitoTEMPO suppresses manoalide-induced MitoSOX generation and γH2AX/8-oxodG DNA damages. This study validates the preferential antiproliferation effect of manoalide and explores the oxidative stress-dependent mechanisms in anti-oral cancer treatment.

scholarly journals Oxidative Stress-Dependent Synergistic Antiproliferation, Apoptosis, and DNA Damage of Ultraviolet-C and Coral-Derived Sinularin Combined Treatment for Oral Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2450
Author(s):  
Sheng-Yao Peng ◽  
Jen-Yang Tang ◽  
Ruei-Nian Li ◽  
Hurng-Wern Huang ◽  
Chang-Yi Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Combined Treatment ◽  
Ultraviolet C ◽  
Oral Cancer Cells ◽  
Stress Dependent ◽  
Oral Cells

Combined treatment is increasingly used to improve cancer therapy. Non-ionizing radiation ultraviolet-C (UVC) and sinularin, a coral Sinularia flexibilis-derived cembranolide, were separately reported to provide an antiproliferation function to some kinds of cancer cells. However, an antiproliferation function using the combined treatment of UVC/sinularin has not been investigated as yet. This study aimed to examine the combined antiproliferation function and explore the combination of UVC/sinularin in oral cancer cells compared to normal oral cells. Regarding cell viability, UVC/sinularin displays the synergistic and selective killing of two oral cancer cell lines, but remains non-effective for normal oral cell lines compared to treatments in terms of MTS and ATP assays. In tests using the flow cytometry, luminescence, and Western blotting methods, UVC/sinularin-treated oral cancer cells exhibited higher reactive oxygen species production, mitochondrial superoxide generation, mitochondrial membrane potential destruction, annexin V, pan-caspase, caspase 3/7, and cleaved-poly (ADP-ribose) polymerase expressions than that in normal oral cells. Accordingly, oxidative stress and apoptosis are highly induced in a combined UVC/sinularin treatment. Moreover, UVC/sinularin treatment provides higher G2/M arrest and γH2AX/8-hydroxyl-2′deoxyguanosine-detected DNA damages in oral cancer cells than in the separate treatments. A pretreatment can revert all of these changes of UVC/sinularin treatment with the antioxidant N-acetylcysteine. Taken together, UVC/sinularin acting upon oral cancer cells exhibits a synergistic and selective antiproliferation ability involving oxidative stress-dependent apoptosis and cellular DNA damage with low toxic side effects on normal oral cells.

scholarly journals Methanol Extract of Usnea barbata Induces Cell Killing, Apoptosis, and DNA Damage against Oral Cancer Cells through Oxidative Stress

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 694
Author(s):  
Jen-Yang Tang ◽  
Kuang-Han Wu ◽  
Yen-Yun Wang ◽  
Ammad Ahmad Farooqi ◽  
Hurng-Wern Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Time Course ◽  
Cell Killing ◽  
Parp Cleavage ◽  
Flow Cytometric ◽  
Oral Cancer Cells

Some lichens provide the resources of common traditional medicines and show anticancer effects. However, the anticancer effect of Usnproliea barbata (U. barbata) is rarely investigated, especially for oral cancer cells. The aim of this study was to investigate the cell killing function of methanol extracts of U. barbata (MEUB) against oral cancer cells. MEUB shows preferential killing against a number of oral cancer cell lines (Ca9-22, OECM-1, CAL 27, HSC3, and SCC9) but rarely affects normal oral cell lines (HGF-1). Ca9-22 and OECM-1 cells display the highest sensitivity to MEUB and were chosen for concentration effect and time course experiments to address its cytotoxic mechanisms. MEUB induces apoptosis of oral cancer cells in terms of the findings from flow cytometric assays and Western blotting, such as subG1 accumulation, annexin V detection, and pancaspase activation as well as poly (ADP-ribose) polymerase (PARP) cleavage. MEUB induces oxidative stress and DNA damage of oral cancer cells following flow cytometric assays, such as reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) production, mitochondrial membrane potential (MMP) depletion as well as overexpression of γH2AX and 8-oxo-2′deoxyguanosine (8-oxodG). All MEUB-induced changes in oral cancer cells were triggered by oxidative stress which was validated by pretreatment with antioxidant N-acetylcysteine (NAC). In conclusion, MEUB causes preferential killing of oral cancer cells and is associated with oxidative stress, apoptosis, and DNA damage.

scholarly journals Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells

2017 ◽  
Vol 8 ◽  
Author(s):  
Hsueh-Wei Chang ◽  
Ruei-Nian Li ◽  
Hui-Ru Wang ◽  
Jing-Ru Liu ◽  
Jen-Yang Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Withaferin A ◽  
Oral Cancer Cells

scholarly journals Soft Coral-Derived Dihydrosinularin Exhibits Antiproliferative Effects Associated with Apoptosis and DNA Damage in Oral Cancer Cells

2021 ◽  
Vol 14 (10) ◽  
pp. 994
Author(s):  
Kun-Han Yang ◽  
Yu-Sheng Lin ◽  
Sheng-Chieh Wang ◽  
Min-Yu Lee ◽  
Jen-Yang Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Growth ◽  
Oral Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Soft Coral ◽  
Oral Cancer Cells

Dihydrosinularin (DHS) is an analog of soft coral-derived sinularin; however, the anticancer effects and mechanisms of DHS have seldom been reported. This investigation examined the antiproliferation ability and mechanisms of DHS on oral cancer cells. In a cell viability assay, DHS showed growth inhibition against several types of oral cancer cell lines (Ca9-22, SCC-9, OECM-1, CAL 27, OC-2, and HSC-3) with no cytotoxic side effects on non-malignant oral cells (HGF-1). Ca9-22 and SCC-9 cell lines showing high susceptibility to DHS were selected to explore the antiproliferation mechanisms of DHS. DHS also causes apoptosis as detected by annexin V, pancaspase, and caspase 3 activation. DHS induces oxidative stress, leading to the generation of reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) and mitochondrial membrane potential (MitoMP) depletion. DHS also induced DNA damage by probing γH2AX phosphorylation. Pretreatment with the ROS scavenger N-acetylcysteine (NAC) can partly counter these DHS-induced changes. We report that the marine natural product DHS can inhibit the cell growth of oral cancer cells. Exploring the mechanisms of this cancer cell growth inhibition, we demonstrate the prominent role DHS plays in oxidative stress.

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

2019 ◽  
Vol 34 (8) ◽  
pp. 891-901 ◽  
Author(s):  
Jen‐Yang Tang ◽  
Sheng‐Yao Peng ◽  
Yuan‐Bin Cheng ◽  
Chun‐Lin Wang ◽  
Ammad Ahmad Farooqi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Ethyl Acetate ◽  
Cancer Cells ◽  
Ethyl Acetate Extract ◽  
Oral Cancer Cells

scholarly journals Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1063
Author(s):  
Tsu-Ming Chien ◽  
Kuang-Han Wu ◽  
Ya-Ting Chuang ◽  
Yun-Chiao Yeh ◽  
Hui-Ru Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Withaferin A ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Dna Damages ◽  
Bladder Cancer Cells ◽  
Stress Dependent

Withaferin A (WFA), the Indian ginseng bioactive compound, exhibits an antiproliferation effect on several kinds of cancer, but it was rarely reported in bladder cancer cells. This study aims to assess the anticancer effect and mechanism of WFA in bladder cancer cells. WFA shows antiproliferation to bladder cancer J82 cells based on the finding of the MTS assay. WFA disturbs cell cycle progression associated with subG1 accumulation in J82 cells. Furthermore, WFA triggers apoptosis as determined by flow cytometry assays using annexin V/7-aminoactinomycin D and pancaspase detection. Western blotting also supports WFA-induced apoptosis by increasing cleavage of caspases 3, 8, and 9 and poly ADP-ribose polymerase. Mechanistically, WFA triggers oxidative stress-association changes, such as the generation of reactive oxygen species and mitochondrial superoxide and diminishment of the mitochondrial membrane potential, in J82 cells. In response to oxidative stresses, mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), superoxide dismutase 1 (SOD1), thioredoxin (TXN), glutathione-disulfide reductase (GSR), quinone dehydrogenase 1 (NQO1), and heme oxygenase 1 (HMOX1), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects. In conclusion, WFA possesses anti-bladder cancer effects by inducing antiproliferation, apoptosis, and DNA damage in an oxidative stress-dependent manner.

Antimycin A shows selective antiproliferation to oral cancer cells by oxidative stress‐mediated apoptosis and DNA damage

2020 ◽  
Vol 35 (11) ◽  
pp. 1212-1224
Author(s):  
Tzu‐Jung Yu ◽  
Che‐Yu Hsieh ◽  
Jen‐Yang Tang ◽  
Li‐Ching Lin ◽  
Hurng‐Wern Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Antimycin A ◽  
Oral Cancer Cells

scholarly journals Nepenthes Ethyl Acetate Extract Provides Oxidative Stress-Dependent Anti-Leukemia Effects

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1410
Author(s):  
Wangta Liu ◽  
Li-Ching Lin ◽  
Pei-Ju Wang ◽  
Yan-Ning Chen ◽  
Sheng-Chieh Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Ethyl Acetate ◽  
Cell Lines ◽  
Ethyl Acetate Extract ◽  
Antioxidant Properties ◽  
Leukemia Cells ◽  
Heme Oxygenase 1 ◽  
Mitochondrial Membrane Depolarization ◽  
Stress Dependent

Several kinds of solvents have been applied to Nepenthes extractions exhibiting antioxidant and anticancer effects. However, they were rarely investigated for Nepenthes ethyl acetate extract (EANT), especially leukemia cells. The purpose of the present study was to evaluate the antioxidant properties and explore the antiproliferation impact and mechanism of EANT in leukemia cells. Five standard assays demonstrated that EANT exhibits antioxidant capability. In the cell line model, EANT dose-responsively inhibited cell viabilities of three leukemia cell lines (HL-60, K-562, and MOLT-4) based on 24 h MTS assays, which were reverted by pretreating oxidative stress and apoptosis inhibitors (N-acetylcysteine and Z-VAD-FMK). Due to similar sensitivities among the three cell lines, leukemia HL-60 cells were chosen for exploring antiproliferation mechanisms. EANT caused subG1 and G1 cumulations, triggered annexin V-detected apoptosis, activated apoptotic caspase 3/7 activity, and induced poly ADP-ribose polymerase expression. Moreover, reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane depolarization were generated by EANT, which was reverted by N-acetylcysteine. The antioxidant response to oxidative stress showed that EANT upregulated mRNA expressions for nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), thioredoxin (TXN), heme oxygenase 1 (HMOX1), and NAD(P)H quinone dehydrogenase 1 (NQO1) genes. Moreover, these oxidative stresses led to DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) and were alleviated by N-acetylcysteine. Taken together, EANT demonstrated oxidative stress-dependent anti-leukemia ability to HL-60 cells associated with apoptosis and DNA damage.

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