scholarly journals Kava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Antonio Celentano ◽  
Callisthenis Yiannis ◽  
Rita Paolini ◽  
Pangzhen Zhang ◽  
Camile S. Farah ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Vitro Assay ◽  
Anticancer Effects

Abstract Kava is a beverage made from the ground roots of the plant Piper Methysticum. Active compounds of Kava have previously been demonstrated to exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. Our aim was to investigate the in vitro effects of the main constituents derived from Kava on oral squamous cell carcinoma (OSCC) activity. Gas chromatography mass spectrometry (GCMS) was used to characterise the main constituents of two Kava preparations. Cell proliferation was assessed in two human OSCC cell lines (H400 and BICR56) and in normal oral keratinocytes (OKF6) treated with the identified Kava constituents, namely Flavokawain A (FKA), Flavokawain B (FKB), yangonin, kavain and methysticin using an MTS in vitro assay. Cell migration at 16 h was assessed using a Transwell migration assay. Cell invasion was measured at 22 h using a Matrigel assay. Cell adhesion was assessed at 90 min with a Cytoselect Adhesion assay. The two Kava preparations contained substantially different concentrations of the main chemical constituents. Treatment of malignant and normal oral keratinocyte cell lines with three of the identified constituents, 10 μg/ml FKA, 2.5 μg/ml FKB and 10 μg/ml yangonin, showed a significant reduction in cell proliferation in both H400 and BICR56 cancer cell lines but not in normal OKF6 cells. Remarkably, the same Kava constituents induced a significant reduction of OSCC cell migration and invasion. We have demonstrated, for the first time, that Kava constituents, FKA, FKB and yangonin have potential anticancer effects on OSCC. This highlights an avenue for further research of Kava constituents in the development of future cancer therapies to prevent and treat OSCC.

scholarly journals Inhibition of Cell Proliferation and MAP Kinase and Akt Pathways in Oral Squamous Cell Carcinoma by Genistein and Biochanin A

2010 ◽  
Vol 7 (3) ◽  
pp. 351-358 ◽  
Author(s):  
Tara L. Johnson ◽  
Maria B. Lai ◽  
James C. K. Lai ◽  
Alok Bhushan
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Squamous Cell ◽  
Biochanin A ◽  
High Morbidity

High morbidity and mortality associated with oral squamous cell carcinoma (OSCC) are largely attributable to late stage diagnosis. Despite significant advances in therapeutic strategies, the five-year survival rate for oral cancer remains at about 50%. A chemopreventive approach may be an effective alternative or adjunct to current therapies. Previous studies have shown anti-tumor effects of isoflavones in several cancers, including oral cancer. However, their mechanisms of action are still unclear. We hypothesized that isoflavones inhibit multiple signaling pathways implicated in oral carcinogenesis. To address our hypothesis, we investigated the effects of three isoflavone derivatives, genistein, biochanin A and daidzein, on SCC15 and SCC25 squamous cell carcinoma cell lines. In cell proliferation experiments, we found that genistein and biochanin A inhibited SCC15 and SCC25 cell growth with an IC50 of 50 μM. We also investigated the effect of isoflavones on ERK and Akt pathways. Our results, from western blot analysis, suggest that both genistein and biochanin A induced decreases in phosphorylation of ERK and Akt at treatment concentrations of 20, 50 and 100 μM. Taken together, our results clearly demonstrate a differential regulation of signaling pathways by various isoflavones in OSCC cell lines. Thus, tumor progression models can be utilized to study the preventive and therapeutic roles of isoflavones in oral cancer cell lines.

Ral GTPase Activation by Downregulation of RalGAP Enhances Oral Squamous Cell Carcinoma Progression

2019 ◽  
Vol 98 (9) ◽  
pp. 1011-1019 ◽  
Author(s):  
P. Gao ◽  
S. Liu ◽  
R. Yoshida ◽  
C.Y. Shi ◽  
S. Yoshimachi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Activation Level ◽  
Ral Gtpase

Ral small GTPases, consisting of RalA and RalB, are members of the Ras family. Their activity is upregulated by RalGEFs. Since several RalGEFs are downstream effectors of Ras, Ral is activated by the oncogenic mutant Ras. Ral is negatively regulated by RalGAP complexes that consist of a catalytic α1 or α2 subunit and its common partner β subunit and similarly regulate the activity of RalA as well as RalB in vitro. Ral plays an important role in the formation and progression of pancreatic and lung cancers. However, the involvement of Ral in oral squamous cell carcinoma (OSCC) is unclear. In this study, we investigated OSCC by focusing on Ral. OSCC cell lines with high Ral activation exhibited higher motility. We showed that knockdown of RalGAPβ increased the activation level of RalA and promoted the migration and invasion of HSC-2 OSCC cells in vitro. In contrast, overexpression of wild-type RalGAPα2 in TSU OSCC cells attenuated the activation level of RalA and inhibited cell migration and invasion. Real-time quantitative polymerase chain reaction analysis of samples from patients with OSCC showed that RalGAPα2 was downregulated in oral cancer tissues as compared with normal epithelia. Among patients with OSCC, those with a lower expression of RalGAPα2 showed a worse overall survival rate. A comparison of DNA methylation and histone modifications of the RalGAPα2 gene in OSCC cell lines suggested that crosstalk among DNA methylation, histone H4Ac, and H3K27me2 was involved in the downregulation of RalGAPα2. Thus, activation of Ral GTPase by downregulation of RalGAP expression via a potential epigenetic mechanism may enhance OSCC progression.

scholarly journals Podoplanin promotes cell migration via the EGF-Src-Cas pathway in oral squamous cell carcinoma cell lines

2012 ◽  
Vol 54 (3) ◽  
pp. 241-250 ◽  
Author(s):  
Harumi Inoue ◽  
Yuji Miyazaki ◽  
Kentaro Kikuchi ◽  
Noriaki Yoshida ◽  
Fumio Ide ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Carcinoma Cell ◽  
Squamous Cell Carcinoma Cell ◽  
Carcinoma Cell Lines

scholarly journals Overexpression ofβ-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Long Li ◽  
Hai-Chao Liu ◽  
Cheng Wang ◽  
Xiqiang Liu ◽  
Feng-Chun Hu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cisplatin Resistance ◽  
Stable Cell Lines ◽  
Abnormal Expression

Abnormal expression ofβ-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression ofβ-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect ofβ-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines withβ-catenin knockin and knockdown. In this study, we found that higher expression level ofβ-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels ofβ-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation ofβ-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism ofβ-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression ofβ-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3β, C-myc, Bcl-2, P-gp, and MRP-1 were involved inβ-catenin-mediated drug resistance. Our findings indicate that the Wnt/β-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.

scholarly journals Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

2022 ◽  
Vol 9 ◽  
Author(s):  
Yixiu Yu ◽  
Jiamei Niu ◽  
Xingwei Zhang ◽  
Xue Wang ◽  
Hongquan Song ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Bioinformatics Analyses ◽  
Gene Set

ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.

scholarly journals miR-146b Functions as an Oncogene in Oral Squamous Cell Carcinoma by Targeting HBP1

2020 ◽  
Vol 19 ◽  
pp. 153303382095940
Author(s):  
Kui Li ◽  
Zheng Zhou ◽  
Ju Li ◽  
Rui Xiang
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Prediction ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
The Impact

Oral squamous cell carcinoma (OSCC) represents more than 90% of all oral cancer and is the most common oral threat around the world. In this study, we examined the roles of miR-146b in OSCC cells. The miR-146b expression in OSCC tissues and cell lines was evaluated by quantitative real-time PCR (qRT-PCR). MTT assay was used to investigate the impact of miR-146b on the growth of OSCC cells in vitro. Transwell assay was utilized to analyze the effect of miR-146b on the migration and invasion of OSCC cells. Target prediction and luciferase assay were employed to demonstrate the interaction between miR-146b and HMG-Box Transcription Factor 1 (HBP1). Western blot was carried out to investigate the protein expressions of HBP1 related genes. miR-146b expression was significantly higher in OSCC tissues and cells compared with paired normal tissues and normal oral keratinocyte cells. Inhibition of miR-146b decreased cell proliferation, migration, and invasion of OSCC cells. Further studies found that HBP1 was a direct target of miR-146b. Co-inhibition of HBP1 reversed the suppressive impact of miR-146b inhibition on OSCC cell proliferation, migration, and invasion. In conclusion-ourresults reveal that miR-146b potentially regulates the proliferation, migration, and invasion of OSCC cells through binding and downregulating HBP1 expression in OSCC cells.

scholarly journals Anticancer effects of valproic acid on oral squamous cell carcinoma via SUMOylation in vivo and in vitro

2016 ◽  
Vol 12 (6) ◽  
pp. 3979-3987 ◽  
Author(s):  
Zhijian Sang ◽  
Yang Sun ◽  
Hong Ruan ◽  
Yong Cheng ◽  
Xiaojun Ding ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Anticancer Effects

scholarly journals Metformin Affects Cancer Regulation and Metabolism of Oral Squamous Cell Carcinoma Partially Through Upregulation of H3K27ac 

2020 ◽  
Author(s):  
Shan Liu ◽  
Congyu Shi ◽  
Xiaoru Hou ◽  
Chunjie Li ◽  
Xiangrui Ma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Histone Modification ◽  
Cell Carcinoma ◽  
Western Blotting ◽  
Squamous Cell ◽  
Underlying Mechanisms

Abstract Objectives Metformin, a first-line drug that has been used for type 2 diabetes treatment, recently attracts broad attention for its therapeutic effects on diverse human cancers. However, its effect and underlying mechanisms in oral squamous cell carcinoma (OSCC) are not well known. Materials and Methods OSCC cells were used to detect the effect of metformin on cell proliferation, colony formation, cell cycle and migration in vitro. Tumor growth of nude mice was conducted to detect the effect of metformin in vivo. Western blotting and immunohistochemistry were used to investigate the effect of metformin on the expression of histone modification in vitro and vivo. The combined effect on cell proliferation and histone modification of metformin and downregulation of EZH2 was detected by CCK8 and western blotting. Additionally, RNA-seq and ChIP-seq was performed to explore the underlying mechanisms of metformin in OSCC.Results Metformin could inhibit OSCC cell proliferation and tumor growth with the increased acetylation at lysine 27 of histone H3 (H3K27ac) in vitro and vivo. The underlying mechanisms were related to cancer regulation and cancer metabolism, affected by the increased H3K27ac. Additionally, metformin could synergize with siRNA-EZH2 to inhibit OSCC cell proliferation independent on the increased H3K27ac.Conclusions Metformin could play anti-cancer role in OSCC progression, with the reprogramming of cancer regulation and metabolism partially regulated by the increased H3K27ac.

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