scholarly journals Contribution of p38 MAPK Pathway to Norcantharidin-Induced Programmed Cell Death in Human Oral Squamous Cell Carcinoma

2019 ◽  
Vol 20 (14) ◽  
pp. 3487 ◽  
Author(s):  
Chi-Hyun Ahn ◽  
Kyoung-Ok Hong ◽  
Bohwan Jin ◽  
WonWoo Lee ◽  
Yun Chan Jung ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
P38 Mapk ◽  
Cell Lines ◽  
Squamous Cell ◽  
Mapk Pathway ◽  
Terminal Deoxynucleotidyl Transferase

Norcantharidin (NCTD), a demethylated analog of cantharidin isolated from blister beetles, has been used as a promising anticancer agent; however, the underlying function of NCTD against human oral squamous cell carcinoma (OSCC) has not been fully understood. Here, this study was aimed to investigate the apoptotic effect and molecular targets of NCTD in human OSCC in vitro and in vivo. The anticancer effects of NCTD and its related molecular mechanisms were evaluated by trypan blue exclusion assay, live/dead assay, western blotting, 4-6-Diamidino-2-Phenylindole (DAPI) staining, flow cytometric analysis, Terminal Deoxynucleotidyl Transferase dUTP Nick end Labeling (TUNEL) assay, and immunohistochemistry. NCTD significantly inhibited cell growth and increased the number of dead cells in HSC-3 and HN22 cell lines. It induced the following apoptotic phenomena: (1) the cleavages of poly (ADP-ribose) polymerase and casepase-3; (2) increase in apoptotic morphological changes (nuclear condensation and fragmentation); (3) increase in annexin V-positive cells or sub-G1 population of cells. NCTD significantly activated the p38 mitogen-activated protein kinase (MAPK) pathway but inactivated the signal transducer and activator of transcription (STAT)3 pathway. A p38 MAPK inhibitor (SB203580) partially attenuated NCTD-induced programmed cell death (apoptosis) in both cell lines, whereas ectopic overexpression of STAT3 did not affect it. NCTD strongly suppressed tumor growth in the tumor xenograft bearing HSC-3 cells, and the number of TUNEL-positive cells increased in NCTD-treated tumor tissues. In addition, NCTD did not cause any histopathological changes in the liver nor the kidney. NCTD induced programmed cell death via the activation of p38 MAPK in OSCC. Therefore, these results suggest that NCTD could be a potential anticancer drug candidate for the treatment of OSCC.

scholarly journals Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin-specific peptidase 9, X-linked in oral squamous cell carcinoma

2018 ◽  
Vol 7 (8) ◽  
pp. 4004-4011 ◽  
Author(s):  
Wu Jingjing ◽  
Guo Wenzheng ◽  
Wen Donghua ◽  
Hou Guangyu ◽  
Zhou Aiping ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Squamous Cell

scholarly journals Cisplatin‐induced programmed cell death ligand‐2 expression is associated with metastasis ability in oral squamous cell carcinoma

2020 ◽  
Vol 111 (4) ◽  
pp. 1113-1123
Author(s):  
Shunichi Sudo ◽  
Hiroshi Kajiya ◽  
Shinji Okano ◽  
Mina Sasaki ◽  
Yuri Katsumata ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Squamous Cell

scholarly journals Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 292-301
Author(s):  
Yong-Xin Cui ◽  
Xian-Shuang Su
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Large Scale ◽  
Meta Analysis ◽  
Human Papilloma Virus Infection ◽  
Clinicopathological Features

AbstractObjectiveProgrammed cell death-ligand 1 (PD-L1) expression has been shown to play important roles in various types of cancer. However, the role of PD-L1 expression has not been conclusively reported in patients with oral squamous cell carcinoma (OSCC). Accordingly, in this meta-analysis, we investigated the clinicopathological value of PD-L1 expression in patients with OSCC.MethodsGoogle Scholar, PubMed, EMBASE, and CNKI databases were searched to find relevant studies published through to September 16, 2019. The relationships between PD-L1 expression in patients with OSCC and clinicopathological features were assessed using risk ratio (RR) and 95% confidence intervals (CIs).ResultsSixteen studies including 1989 participants were included. The results indicated that high PD-L1 expression was correlated with sex (RR = 1.28, 95% CI: 1.16–1.42, P < 0.001), N stage (RR = 1.19, 95% CI: 1.06–1.33, P = 0.003), M stage (RR = 1.64, 95% CI: 1.01–2.66, P = 0.044), low differentiation (RR = 1.16, 95% CI: 1.01–1.33, P = 0.034), and human papilloma virus infection (RR = 1.38, 95% CI: 1.14–1.68, P = 0.001), but unrelated to TNM stage or T stage. There was no significant publication bias in the studies included in this analysis.ConclusionsThis meta-analysis revealed that high PD-L1 expression in patients with OSCC was correlated with clinicopathological features. Further large-scale studies are necessary to confirm our results.

scholarly journals Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma

2010 ◽  
Vol 9 (1) ◽  
pp. 238 ◽  
Author(s):  
Patricia P Reis ◽  
Miranda Tomenson ◽  
Nilva K Cervigne ◽  
Jerry Machado ◽  
Igor Jurisica ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Programmed Cell Death ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Programmed Cell Death 4

Programmed cell death-ligand 1 expression in oral squamous cell carcinoma is associated with an inflammatory phenotype

Pathology ◽  
2016 ◽  
Vol 48 (6) ◽  
pp. 574-580 ◽  
Author(s):  
Laveniya Satgunaseelan ◽  
Ruta Gupta ◽  
Jason Madore ◽  
Noel Chia ◽  
Trina Lum ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Inflammatory Phenotype

scholarly journals Dual Targeting of the p38 MAPK-HO-1 Axis and cIAP1/XIAP by Demethoxycurcumin Triggers Caspase-Mediated Apoptotic Cell Death in Oral Squamous Cell Carcinoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 703 ◽  
Author(s):  
Ming-Hsien Chien ◽  
Wei-En Yang ◽  
Yi-Chieh Yang ◽  
Chia-Chi Ku ◽  
Wei-Jiunn Lee ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
P38 Mapk ◽  
Squamous Cell ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Heme Oxygenase 1 ◽  
Caspase 8

Demethoxycurcumin (DMC) is a curcumin analogue with better stability and higher aqueous solubility than curcumin after oral ingestion and has the potential to treat diverse cancers, including oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the anticancer effects and underlying mechanisms of DMC against OSCC. We found that DMC suppressed cell proliferation via simultaneously inducing G2/M-phase arrest and cell apoptosis. Mechanistic investigations found that the downregulation of cellular IAP 1 (cIAP1)/X-chromosome-linked IAP (XIAP) and upregulation of heme oxygenase-1 (HO-1) were critical for DMC-induced caspase-8/-9/-3 activation and apoptotic cell death. Moreover, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK)1/2 were activated by DMC treatment in OSCC cells, and only the inhibition of p38 MAPK significantly abolished DMC-induced HO-1 expression and caspase-8/-9/-3 activation. The analyses of clinical datasets revealed that patients with head and neck cancers expressing high HO-1 and low cIAP1 had the most favorable prognoses. Furthermore, a combinatorial treatment of DMC with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, significantly enhanced the inhibitory effect of gefitinib on the proliferation of OSCC cells. Overall, the current study supported a role for DCM as part of a therapeutic approach for OSCC through suppressing IAPs and activating the p38-HO-1 axis.

scholarly journals Anticancer Efficacy of Nonthermal Plasma Therapy Combined with PD-L1 Antibody Conjugated Gold Nanoparticles on Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 (10) ◽  
pp. 4559
Author(s):  
Jinyoung Park ◽  
Yoon-Seo Jang ◽  
Jeong-Hae Choi ◽  
Miheon Ryu ◽  
Gyoo-Cheon Kim ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Nonthermal Plasma ◽  
Therapeutic Effects ◽  
Hacat Cells ◽  
Plasma Therapy

Combination therapies for the treatment of oral squamous cell carcinoma have been studied extensively and represent a synergistic approach with better outcomes than monotherapy. In this study, a novel combination therapy was investigated using gold nanoparticles (GNP) conjugated to programmed cell death protein ligand 1 (PD-L1) antibodies and nonthermal plasma (NTP). The present study describes the effectiveness of NTP using PD-L1 antibody conjugated to GNP in PD-L1 expressing SCC-25 cells, an oral squamous cell carcinoma line. Immunocytochemistry revealed higher levels of PD-L1 expression and an increase in the selective uptake of PD-L1 antibody + GNP on SCC-25 cells compared to HaCaT cells. In addition, cell viability analyses confirmed higher levels of cell death of SCC-25 cells after treatment with PD-L1 antibody, GNP, and NTP compared to HaCaT cells. Among the experimental groups, the highest cell death was observed upon treatment with PD-L1 antibody + GNP + NTP. Following the Western blot analysis and immunofluorescence staining, the expression of apoptosis-related proteins was found to increase after treatment with PD-L1 antibody + GNP + NTP among the other experimental groups. In conclusion, the treatment of SCC-25 cells with PD-L1 antibody + GNP + NTP significantly increased the number of dead cells compared to other experimental groups. The results of this in vitro study confirmed the therapeutic effects of PD-L1 antibody + GNP + NTP treatment on oral squamous cell carcinoma.

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