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.

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 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.

792: Role of Oxidative Stress in Tumorigenic Potential of Bladder Cancer Cells

2005 ◽  
Vol 173 (4S) ◽  
pp. 214-215 ◽  
Author(s):  
Daniel Cho ◽  
Xiao Fang Ha ◽  
J. Andre Melendez ◽  
Louis J. Giorgi ◽  
Badar M. Mian
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Tumorigenic Potential ◽  
Bladder Cancer Cells

Non-canonical Functions of Telomerase Reverse Transcriptase: Emerging Roles and Biological Relevance

2020 ◽  
Vol 20 (6) ◽  
pp. 498-507 ◽  
Author(s):  
Connor A.H. Thompson ◽  
Judy M.Y. Wong
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Reverse Transcriptase ◽  
Cancer Cells ◽  
Telomere Length ◽  
Telomere Maintenance ◽  
Telomerase Reverse Transcriptase ◽  
Alternative Mechanism ◽  
Dependent Manner ◽  
Mitochondrial Integrity

Increasing evidence from research on telomerase suggests that in addition to its catalytic telomere repeat synthesis activity, telomerase may have other biologically important functions. The canonical roles of telomerase are at the telomere ends where they elongate telomeres and maintain genomic stability and cellular lifespan. The catalytic protein component Telomerase Reverse Transcriptase (TERT) is preferentially expressed at high levels in cancer cells despite the existence of an alternative mechanism for telomere maintenance (alternative lengthening of telomeres or ALT). TERT is also expressed at higher levels than necessary for maintaining functional telomere length, suggesting other possible adaptive functions. Emerging non-canonical roles of TERT include regulation of non-telomeric DNA damage responses, promotion of cell growth and proliferation, acceleration of cell cycle kinetics, and control of mitochondrial integrity following oxidative stress. Non-canonical activities of TERT primarily show cellular protective effects, and nuclear TERT has been shown to protect against cell death following double-stranded DNA damage, independent of its role in telomere length maintenance. TERT has been suggested to act as a chromatin modulator and participate in the transcriptional regulation of gene expression. TERT has also been reported to regulate transcript levels through an RNA-dependent RNA Polymerase (RdRP) activity and produce siRNAs in a Dicer-dependent manner. At the mitochondria, TERT is suggested to protect against oxidative stress-induced mtDNA damage and promote mitochondrial integrity. These extra-telomeric functions of TERT may be advantageous in the context of increased proliferation and metabolic stress often found in rapidly-dividing cancer cells. Understanding the spectrum of non-canonical functions of telomerase may have important implications for the rational design of anti-cancer chemotherapeutic drugs.

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 Oxidative Stress Sensitizes Bladder Cancer Cells to TRAIL Mediated Apoptosis by Down-Regulating Anti-Apoptotic Proteins

2009 ◽  
Vol 182 (3) ◽  
pp. 1178-1185 ◽  
Author(s):  
Shai J. White-Gilbertson ◽  
Laura Kasman ◽  
John McKillop ◽  
Tejas Tirodkar ◽  
Ping Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Bladder Cancer Cells ◽  
Apoptotic Proteins

scholarly journals Antitumor Effect of IL-2 and TRAIL Proteins Expressed by Recombinant Salmonella in Murine Bladder Cancer Cells

2021 ◽  
Vol 55 (4) ◽  
pp. 460-476
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cell Membrane ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Morphology ◽  
Antitumor Effect ◽  
Interleukin 2 ◽  
Continuous Increase ◽  
Bladder Cancer Cells

Background/Aims: Cancer is the second most deadly disease in the world. The bladder cancer is one of the most aggressive types and shows a continuous increase in the number of cases. The use of bacteria as live vectors to deliver molecules directly to the tumor is a promising tool and has been used as an adjuvant treatment against several types of cancer. The aim of this study was to investigate the antitumor effect of Interleukin 2 (IL-2), TNF-related apoptosis-inducing ligand (TRAIL) and protein MIX against murine bladder cancer cells, lineage MB49. Methods: The attenuated Salmonella strain SL3261 was transformed by inserting the IL-2 and TRAIL genes. The effects of proteins on cell viability (MTT method), cell morphology (optical microscopy), cell recovery (clonogenic assay), cell membrane (lactate dehydrogenase release - LDH), on oxidative stress pathway (levels of nitric oxide, NO) and apoptosis (flow cytometry and high resolution epifluorescence images) were evaluated at intervals of 24 and 48 hours of action. Results: The results showed that there was a decrease in cell viability via damage to the cell membrane, alteration of cell morphology, non-recovery of cells, increase in the production of NO and incubate for of cells in the state of apoptosis in the two periods analyzed. Conclusion: The data presented suggest that IL-2, TRAIL and their MIX proteins in MB49 cells have cytotoxic potential and that this is associated with oxidative stress and apoptosis pathways. These results may contribute to the development of new therapeutic strategies for bladder cancer.

scholarly journals Tannic Acid Induces Apoptosis In Bladder Cancer Cells Via Mitochondrial-Dependent And AKT Pathway

2021 ◽  
Author(s):  
Ming-Cheng Chen ◽  
Ann Seles S ◽  
Bharath Kumar Velmurugan ◽  
Chiung-Hung Hsu ◽  
Cecilia Hsuan Day ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Tannic Acid ◽  
Significant Inhibition ◽  
Stem Cell Markers ◽  
Dependent Manner ◽  
Anti Cancer ◽  
Bladder Cancer Cells ◽  
Urothelial Bladder ◽  
Anti Fungal

Abstract Urothelial bladder cancer is rapidly spreading across Western countries, and therapy has shown little-to-moderate effects on bladder cancer. Thus, focusing on curbing cancer incidence has become crucial. In this study, we examined the effects of tannic acid, a polyphenol with anti-fungal and anti-cancer effects, on UMUC3 bladder cancer cells. UMUC3 cells were exposed to tannic acid for 24 hours, following which we observed significant inhibition of cell proliferation. Additionally, flow cytometry and TUNEL assay revealed that tannic acid induces apoptosis in UMUC3 cells in a dose-dependent manner. Furthermore, tannic acid treatment upregulated the expression of cleaved caspase-3 which further confirmed induction of apoptosis in UMUC3 cells by treatment with tannic acid. TA treatment decreased stem cell markers expression such as SOX2, OCT4, and NANOG. Together, these results showed that tannic acid can promote apoptosis; therefore, it may have potential as treatment for bladder cancer.

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