scholarly journals FLLL32 Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells by Regulating the p38 Pathway

2021 ◽  
Vol 22 (21) ◽  
pp. 11860
Author(s):  
Chun-Wen Su ◽  
Chun-Yi Chuang ◽  
Yi-Tzu Chen ◽  
Wei-En Yang ◽  
Yi-Ping Pan ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Mapk Signaling ◽  
Heme Oxygenase 1 ◽  
Synthetic Analog ◽  
Oral Cancer Cells ◽  
P38 Pathway

Oral cancer is the most common oral malignant tumor in Taiwan. Although there exist several methods for treatment, oral cancer still has a poor prognosis and high recurrence. FLLL32, a synthetic analog of curcumin with antitumor activity, is currently known to induce melanoma apoptosis and inhibit tumor growth in various cancers. However, few studies have examined the mechanisms of FLLL32 in oral cancer. In this study, we explore whether FLLL32 induces apoptosis in oral cancer. We determined that FLLL32 can inhibit the cell viability of oral cancer. Next, we analyzed the effect of FLLL32 on the cell cycle of oral cancer cells and observed that the proportion of cells in the G2/M phase was increased. Additionally, annexin-V/PI double staining revealed that FLLL32 induced apoptosis in oral cancer cells. Data from the Human Apoptosis Array revealed that FLLL32 increases the expression of cleaved caspase-3 and heme oxygenase-1 (HO-1). FLLL32 activates proteins such as caspase-8, caspase-9, caspase-3, PARP, and mitogen-activated protein kinases (MAPKs) in apoptosis-related molecular mechanisms. Moreover, by using MAPK inhibitors, we suggest that FLLL32 induces the apoptosis of oral cancer cells through the p38 MAPK signaling pathway. In conclusion, our findings suggest that FLLL32 is a potential therapeutic agent for oral cancer by inducing caspase-dependent apoptosis and HO-1 activation through the p38 pathway. We believe that the activation of HO-1 and the p38 pathway by FLLL32 represent potential targets for further research in oral cancer.

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

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
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.

scholarly journals Magnolol Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells through JNK1/2 and p38 Pathways

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1295
Author(s):  
Yi-Tzu Chen ◽  
Chiao-Wen Lin ◽  
Chun-Wen Su ◽  
Wei-En Yang ◽  
Chun-Yi Chuang ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cancer Cell Lines ◽  
Heme Oxygenase 1 ◽  
Western Blot Assay ◽  
Oral Cancer Cell

Magnolol is a natural compound extracted from Chinese herbal medicine and can induce apoptosis in numerous types of cancer cells. However, the molecular mechanisms of magnolol in oral cancer are still unclear. In this study, we investigated the anti-cancer effects and underlying mechanisms of magnolol in human oral cancer cell lines. Our results exhibited that magnolol inhibited the cell proliferation via inducing the sub-G1 phase and cell apoptosis of HSC-3 and SCC-9 cells. The human apoptosis array and Western blot assay showed that magnolol increased the expression of cleaved caspase-3 proteins and heme oxygenase-1 (HO-1). Moreover, we proved that magnolol induces apoptosis in oral cancer cell lines via the c-Jun N-terminal kinase (JNK)1/2 and p38 pathways. Overall, the current study supports the role for magnolol as a therapeutic approach for oral cancer through JNK1/2- and p38-mediated caspase activation.

scholarly journals Selective apoptotic cell death effects of oral cancer cells treated with destruxin B

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Rosa Huang Liu ◽  
Shih-Pin Chen ◽  
Tsong-Ming Lu ◽  
Wei-Yu Tsai ◽  
Chung-Hung Tsai ◽  
...  
Keyword(s):  
Cell Death ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Oral Cancer Cells

scholarly journals MiR-219-5p is Involved in the Proliferation, Migration and Invasion of Oral Cancer Through SOX5 Regulation

2021 ◽  
Author(s):  
Ting Zhou ◽  
Ying He ◽  
Xiao-Han Dong ◽  
Bo Chen ◽  
Jun Ton ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Rapid Progression ◽  
Invasion And Migration ◽  
Oral Cancer Cells

Abstract Purpose Oral cancer has the characteristics of rapid progression, wide invasion and poor prognosis, which induces higher mortality in the patients. At present, there are about 300 thousand new cases of oral cell carcinoma worldwide. Particularly, the incidence rate of oral cancer in China is relatively high. Therefore, it urgently needs to understand the pathogenesis of oral cancer and molecular mechanisms underlying. Abnormal regulation of miR-219-5p is present in various types of cancer. However, the relationship between miR-219-5p and its targets in oral cancer has not been well evaluated. Methods Western blotting and Quantitative RT-PCR were used to detect the expression of SOX5 in oral cancer tissues.Migration ,cell proliferation,and invasion were detected using CCK8 assay,Conlony formation assay and Transwell assays .The interaction between SOX5 and miR-219-5p and oral cancer was confirmed using dual-luciferase reporter assays.Result This study aims to investigate the possible roles of miR-219-5p and its potential target gene, SOX5, in the progress of oral cancer. Our data showed that the high miR-219-5p and low SOX5 expression levels were associated with improved survival rates in patients. miR-219-5p level was negatively correlated with the expression of SOX5. Genetic analysis and luciferase assay revealed that the miR-291-5p regulated SOX5 expression by targeting the 3'-UTR region of SOX5 mRNA. Functionally, we confirmed that miR-219-5p mimics inhibited SOX5 expression and suppressed the proliferation, colony formation ability, invasion and migration of oral cancer cells, SCC4 and SCC9. In contrast, inhibition of miR-219-5p increased SOX5 levels and promoted the vitality and mobility of oral cancer cells. Furthermore, special siRNA targeting SOX5 partially neutralized the effects of miR-219-5p inhibitor. Conclusions This study demonstrates that miR-219-5p may inhibit the proliferation, migration and invasion of oral cancer by targeting the expression of SOX5, which provided novel candidates for clinic prognosis and/or therapy.

scholarly journals Low Concentration of Withaferin a Inhibits Oxidative Stress-Mediated Migration and Invasion in Oral Cancer Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 777 ◽  
Author(s):  
Tzu-Jung Yu ◽  
Jen-Yang Tang ◽  
Fu Ou-Yang ◽  
Yen-Yun Wang ◽  
Shyng-Shiou F. Yuan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Withaferin A ◽  
Migration And Invasion ◽  
Heme Oxygenase 1 ◽  
Antioxidant Genes ◽  
Low Concentration ◽  
Oral Cancer Cells

Withaferin A (WFA) has been reported to inhibit cancer cell proliferation based on high cytotoxic concentrations. However, the low cytotoxic effect of WFA in regulating cancer cell migration is rarely investigated. The purpose of this study is to investigate the changes in migration and mechanisms of oral cancer Ca9-22 cells after low concentrations of WFA treatment. WFA under 0.5 μM at 24 h treatment shows no cytotoxicity to oral cancer Ca9-22 cells (~95% viability). Under this condition, WFA triggers reactive oxygen species (ROS) production and inhibits 2D (wound healing) and 3D cell migration (transwell) and Matrigel invasion. Mechanically, WFA inhibits matrix metalloproteinase (MMP)-2 and MMP-9 activities but induces mRNA expression for a group of antioxidant genes, such as nuclear factor, erythroid 2-like 2 (NFE2L2), heme oxygenase 1 (HMOX1), glutathione-disulfide reductase (GSR), and NAD(P)H quinone dehydrogenase 1 (NQO1)) in Ca9-22 cells. Moreover, WFA induces mild phosphorylation of the mitogen-activated protein kinase (MAPK) family, including extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 expression. All WFA-induced changes were suppressed by the presence of ROS scavenger N-acetylcysteine (NAC). Therefore, these results suggest that low concentration of WFA retains potent ROS-mediated anti-migration and -invasion abilities for oral cancer cells.

scholarly journals Effect of protein kinase C alpha, caspase-3, and survivin on apoptosis of oral cancer cells induced by staurosporine1

2005 ◽  
Vol 26 (11) ◽  
pp. 1365-1372 ◽  
Author(s):  
Yu-xia ZHANG ◽  
Shi-bin YU ◽  
Jing-ping OU-YANG ◽  
Dong XIA ◽  
Min WANG ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Kinase C ◽  
Protein Kinase C Alpha ◽  
Oral Cancer Cells

scholarly journals PlatyphyllenoneExerts Anti-Metastatic Effects on Human Oral Cancer Cells by Modulating Cathepsin L Expression, MAPK Pathway and Epithelial–Mesenchymal Transition

2021 ◽  
Vol 22 (9) ◽  
pp. 5012
Author(s):  
V. Bharath Kumar ◽  
Jen-Tsun Lin ◽  
B. Mahalakshmi ◽  
Yi-Ching Chuang ◽  
Hsin-Yu Ho ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mapk Pathway ◽  
Cathepsin L ◽  
Mapk Signaling ◽  
Cancer Prognosis ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Oral Cancer Cells

Advanced-stage oral cancers with lymph node metastasis are associated with poor prognosis and a high mortality rate. Although recent advancement in cancer treatment has effectively improved the oral cancer prognosis, the majority of therapeutic interventions are highly expensive and are associated with severe sideeffects. In the present study, we studied the efficacy of a diarylheptanoid derivative, platyphyllenone, in modulating the metastatic potential of human oral cancer cells. Specifically, we treated the human oral cancer cells (FaDu, Ca9-22, and HSC3) with different concentrations of platyphyllenone and measured the cell proliferation, migration, and invasion. The study findings revealed that platyphyllenonesignificantly inhibited the motility, migration, and invasion of human oral cancer cells. Mechanistically, platyphyllenone reduced p38 phosphorylation, decreased β-catenin and Slug, increased E-cadherin expression, and reduced cathepsin L expression, which collectively led to a reduction in cancer cell migration and invasion. Taken together, our study indicates that platyphyllenone exerts significant anti-metastatic effects on oral cancer cells by modulating cathepsin L expression, the MAPK signaling pathway, and the epithelial–mesenchymal transition process.

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 CCL18-NIR1/GPR3 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signalling pathway

2019 ◽  
Author(s):  
Guodong Chen ◽  
Xiao Jiang ◽  
Xiang Sun ◽  
Zhijie Huang ◽  
Xianghuai Zheng ◽  
...  
Keyword(s):  
Cell Growth ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Receptor Expression ◽  
Mesenchymal Transition ◽  
Specific Receptors ◽  
Oral Cancer Cells ◽  
Stat3 Signalling

Abstract Background Chemokine (C-C motif) ligand 18 (CCL18) affects the malignant progression of varying cancers by activating chemokine receptors. Our previous study have shown that CCL18 promotes hyperplasia and invasiveness of oral cancer cells; however, the cognate receptors of CCL18 involved in the pathogenesis of oral squamous cell carcinoma (OSCC) has not yet been identified. This study aimed to investigate the underlying molecular mechanisms through which CCL18 promotes OSCC progression by binding to specific functional receptors.Methods The properties of CCL18 receptors (i.e., NIR1, CCR6, CCR8, and GPR3) in OSCC were detected by conducting western blotting, immunofluorescence, and immunocytochemistry assays. The binding between CCL18 and its receptors was verified by performing coimmunoprecipitation (CO-IP) assays. The χ2 test was applied to analyze the relationship between CCL18 receptor expression patterns and clinicopathological factors. Recombinant CCL18 (rCCL18) and receptor siRNA were used to confirm the effects of CCL18 receptor axis on the morphology of cancer cells (i.e., proliferation, and metastasis), epithelial-mesenchymal transition (EMT) and the expression of the JAK2/STAT3 signalling pathway.Results NIR1 and GPR3 as specific receptors of CCL18 in OSCC were found to be significantly increased and positively related to the TNM stage of OSCC patients. rCCL18 induced phenotype alterations of oral cancer cells including cell growth, metastasis, and EMT. Knockdown of NIR1 and/or GPR3 expression could block the effects of rCCL18-induced OSCC. Furthermore, JAK2/STAT3 signalling was confirmed to be a downstream pathway of the CCL18-NIR1/GPR3 axis.Conclusion CCL18 can promote the progression of OSCC by binding specific receptors (NIR1 and GPR3), and the CCL18-receptor signalling can activate JAK2/STAT3 pathway. The identification of the mechanisms of CCL18 promoting OSCC progression could implicate potential therapeutic targets for treating oral cancer.

scholarly journals Tiazofurin inhibits oral cancer growth in vitro and in vivo via upregulation of miR-204 expression

2020 ◽  
Vol 19 (7) ◽  
pp. 1377-1382
Author(s):  
Xiaoying Tang ◽  
Aimin Zhao ◽  
Yanhuan Hong
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Cancer Growth ◽  
Caspase 9 ◽  
Diphenyltetrazolium Bromide ◽  
Oral Cancer Cells

Purpose: To investigate the effect of tiazofurin on proliferation and growth of oral cancer cells, and the associated mechanism(s) of action.Methods: The effect of tiazofurin on the cytotoxicity of SCC-VII and SCC-25 oral cancer cells were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while cell apoptosis was determined by flow cytometry. Western blotting was used for assaying proteinexpressions.Results: Tiazofurin inhibited the viability of the oral cancer cells in a concentration-based manner (p < 0.05). Tiazofurin treatment at a dose of 2.0 μM reduced the proliferation of SCC-VII and SCC-25 cells to 25 and 22 %, respectively. Apoptosis was significantly increased in SCC-VII and SCC-25 cells by tiazofurin treatment, relative to untreated cells (p < 0 .05). Tiazofurin also increased the activation levels of caspase-3 and caspase-9 and downregulated the expressions of p-Akt and p-mTOR in the two cancer cell lines. Moreover, miR-204 expression was significantly promoted in the tiazofurin-treated cells, when compared to control (p < 0 .05). In SCC-VII cells, treatment with tiazofurin suppressed Factin expression, relative to control.Conclusion: These results demonstrate that tiazofurin inhibits the viability and proliferation of SCC-VII and SCC-25 cancer cells via induction of apoptosis and activation of caspase-3/caspase-9. Moreover, tiazofurin targets Akt/mTOR pathway, and upregulats the expressions of F-actin and miR-204 in the oral carcinoma cells. These findings suggest that tiazofurin has a potential for use as an effective treatment for oral cancer. Keywords: Oral cancer, Tiazofurin, Apoptosis, Caspase, Cytotoxicity

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