PARP inhibitor Olaparib Enhances the Apoptotic Potentiality of Curcumin by Increasing the DNA Damage in Oral Cancer Cells through Inhibition of BER Cascade

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.

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WEE1 Kinase Inhibition Reverses DNA Damage Checkpoint Activation to Sensitize Oral Cancer Cells to Immunotherapy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2017.12.296 ◽

2018 ◽

Vol 100 (5) ◽

pp. 1315-1316

Author(s):

C.T. Allen

Keyword(s):

Dna Damage ◽

Oral Cancer ◽

Cancer Cells ◽

Dna Damage Checkpoint ◽

Checkpoint Activation ◽

Kinase Inhibition ◽

Wee1 Kinase ◽

Oral Cancer Cells

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

Frontiers in Physiology ◽

10.3389/fphys.2017.00634 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 30

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

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Bufalin Induces Mitochondria-Dependent Apoptosis in Pancreatic and Oral Cancer Cells by Downregulating hTERT Expression via Activation of the JNK/p38 Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/546210 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Xin Tian ◽

Shundong Dai ◽

Jing Sun ◽

Shenyi Jiang ◽

Chengguang Sui ◽

...

Keyword(s):

Dna Damage ◽

Oral Cancer ◽

Cell Viability ◽

Cancer Cells ◽

P38 Mapk ◽

Molecular Mechanisms ◽

Mapk Pathway ◽

Ros Production ◽

Oral Cancer Cells ◽

P38 Pathway

Bufalin, a digoxin-like active component of the traditional Chinese medicine Chan Su, exhibits potent antitumor activities in many human cancers. Bufalin induces mitochondria-dependent apoptosis in cancer cells, but the detailed molecular mechanisms are largely unknown. hTERT, the catalytic subunit of telomerase, protects against mitochondrial damage by binding to mitochondrial DNA and reducing mitochondrial ROS production. In the present study, we investigated the effects of bufalin on the cell viability, ROS production, DNA damage, and apoptosis of CAPAN-2 human pancreatic and CAL-27 human oral cancer cells. Bufalin reduced CAPAN-2 and CAL-27 cell viability with IC50values of 159.2 nM and 122.6 nM, respectively. The reduced cell viability was accompanied by increased ROS production, DNA damage, and apoptosis and decreased expression of hTERT. hTERT silencing in CAPAN-2 and CAL-27 cells by siRNA resulted in increased caspase-9/-3 cleavage and DNA damage and decreased cell viability. Collectively, these data suggest that bufalin downregulates hTERT to induce mitochondria-dependent apoptosis in CAPAN-2 and CAL-27 cells. Moreover, bufalin increased the phosphorylation of JNK and p38-MAPK in CAPAN-2 and CAL-27 cells, and blocking the JNK/p38-MAPK pathway using the JNK inhibitor SP600125 or the p38-MAPK inhibitor SB203580 reversed bufalin-induced hTERT downregulation. Thus, the JNK/p38 pathway is involved in bufalin-induced hTERT downregulation and subsequent induction of apoptosis by the mitochondrial pathway.

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Benzyl isothiocyanate promotes apoptosis of oral cancer cells via an acute redox stress-mediated DNA damage response

Food and Chemical Toxicology ◽

10.1016/j.fct.2016.09.028 ◽

2016 ◽

Vol 97 ◽

pp. 336-345 ◽

Cited By ~ 7

Author(s):

Yao-Tsung Yeh ◽

Yen-Nien Hsu ◽

Sheng-Yun Huang ◽

Jian-Sheng Lin ◽

Zi-Feng Chen ◽

...

Keyword(s):

Dna Damage ◽

Oral Cancer ◽

Cancer Cells ◽

Dna Damage Response ◽

Redox Stress ◽

Benzyl Isothiocyanate ◽

Damage Response ◽

Oral Cancer Cells

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

Pharmaceuticals ◽

10.3390/ph14100994 ◽

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.

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

Cancers ◽

10.3390/cancers11091303 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1303 ◽

Cited By ~ 8

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.

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