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.

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 Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)—The Effect of Celecoxib

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 136 ◽  
Author(s):  
Natalia Tołoczko-Iwaniuk ◽  
Dorota Dziemiańczyk-Pakieła ◽  
Katarzyna Celińska-Janowicz ◽  
Ilona Zaręba ◽  
Agnieszka Klupczyńska ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Histological Grade ◽  
Clinical Stage ◽  
High Morbidity ◽  
Proline Metabolism ◽  
Proline Concentration

Background: Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatment optimisation. Proline metabolism may prove to be of importance in the search for new treatment modalities. Methods: To evaluate the significance of proline metabolism in the development of oral cancer, proline concentration was assessed in oral cancer tissue and normal oral mucosa. The results were compared to the clinical stage and histological grade of the tumours. Moreover, the expression of proteins involved in proline metabolism via proline dehydrogenase/oxidase (PRODH/POX, PPARγ, HIF1-α) was determined. In the next stage of the study, conducted on cell lines of tongue cancer treated with celecoxib, the aforementioned factors involved in proline metabolism were evaluated. Cellular viability and cell proliferation, as well as apoptosis, were also assessed. Results: Our research results indicate that a high intracellular proline concentration and expression of factors involved in its metabolism correlate with the clinical stage and histological grade of oral cancer. Moreover, we are the first researchers to demonstrate that celecoxib can affect proline metabolism, causing an increase in pro-apoptotic factors (PRODH/POX, PPARγ), reducing the expression of HIF-1α and activating apoptosis. Conclusions: Proline metabolism, due to its involvement in the process of apoptosis, can be of great importance in anticancer therapy. It appears that celecoxib, which influences the PRODH/POX pathway, may be a promising therapeutic compound in oral cancer treatment.

scholarly journals Cisplatin Plus Cetuximab Inhibits Cisplatin-Resistant Human Oral Squamous Cell Carcinoma Cell Migration and Proliferation but Does Not Enhance Apoptosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8167
Author(s):  
Hyeong Sim Choi ◽  
Young-Kyun Kim ◽  
Pil-Young Yun
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Motility ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cisplatin Resistance ◽  
Resistant Cells

Cisplatin is among the most widely used anticancer drugs used in the treatment of several malignancies, including oral cancer. However, cisplatin treatment often promotes chemical resistance, subsequently causing treatment failure. Several studies have shown that epidermal growth factor receptors (EGFRs) play a variety of roles in cancer progression and overcoming cisplatin resistance. Therefore, this study focused on EGFR inhibitors used in novel targeted therapies as a method to overcome this resistance. We herein aimed to determine whether the combined effects of cisplatin and cetuximab could enhance cisplatin sensitivity by inhibiting the epithelial-to-mesenchymal transition (EMT) process in cisplatin-resistant cells. In vitro analyses of three cisplatin-resistant oral squamous cell carcinoma cells, which included cell proliferation assay, combination index calculation, cell cytotoxicity assay, live/dead cell count assay, Western blot assay, propidium iodide staining assay, scratch assay, and qRT-PCR assay were then conducted. Our results showed that a cisplatin/cetuximab combination treatment inhibited cell proliferation, cell motility, and N-cadherin protein expression but induced E-cadherin and claudin-1 protein expression. Although the combination of cisplatin and cetuximab did not induce apoptosis of cisplatin-resistant cells, it may be useful in treating oral cancer patients with cisplatin resistance given that it controls cell motility and EMT-related proteins.

scholarly journals Association of ATG4B and Phosphorylated ATG4B Proteins with Tumorigenesis and Prognosis in Oral Squamous Cell Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1854 ◽  
Author(s):  
Pei-Feng Liu ◽  
Hung-Chih Chen ◽  
Jin-Shiung Cheng ◽  
Wei-Lun Tsai ◽  
Huai-Pao Lee ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Protein Levels ◽  
Oral Cancer Cells

Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer death worldwide due to the limited availability of biomarkers and therapeutic targets. Autophagy related protease 4B (ATG4B) is an essential protease for the autophagy machinery, and ATG4B phosphorylation at Ser383/392 increases its proteolytic activity. ATG4B expression and activation are crucial for cancer cell proliferation and invasion. However, the clinical relevance of ATG4B and phospho-Ser383/392-ATG4B for OSCC remains unknown, particularly in buccal mucosal SCC (BMSCC) and tongue SCC (TSCC). With a tissue microarray comprising specimens from 498 OSCC patients, including 179 BMSCC and 249 TSCC patients, we found that the protein levels of ATG4B and phospho-Ser383/392-ATG4B were elevated in the tumor tissues of BMSCC and TSCC compared with those in adjacent normal tissues. High protein levels of ATG4B were significantly associated with worse disease-specific survival (DSS) in OSCC patients, particularly in patients with tumors at advanced stages. In contrast, phospho-Ser383/392-ATG4B expression was correlated with poor disease-free survival (DFS) in TSCC patients. Moreover, ATG4B protein expression was positively correlated with phospho-Ser383/392-ATG4B expression in both BMSCC and TSCC. However, high coexpression levels of ATG4B and phospho-Ser383/392-ATG4B were associated with poor DFS only in TSCC patients, whereas they had no significant association with DSS in BMSCC and TSCC patients. In addition, silencing ATG4B with an antisense oligonucleotide (ASO) or small interfering RNA (siRNA) diminished cell proliferation of TW2.6 and SAS oral cancer cells. Further, knockdown of ATG4B reduced cell migration and invasion of oral cancer cells. Taken together, these findings suggest that ATG4B might be a biomarker for diagnosis/prognosis of OSCC and a potential therapeutic target for OSCC patients.

scholarly journals MicroRNA-99a-5p suppresses cell proliferation, migration, and invasion by targeting isoprenylcysteine carboxylmethyltransferase in oral squamous cell carcinoma

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052093903
Author(s):  
Xiang Sun ◽  
Huixin Yan
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Isoprenylcysteine Carboxylmethyltransferase

Background MicroRNA (miR)-99a-5p acts as a tumor suppressor in several tumors, including bladder cancer and breast cancer, but its biological function in oral squamous cell carcinoma (OSCC) is poorly understood. Methods miR-99a-5p expression was determined in OSCC tissues and cell lines using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell proliferation was assessed by the Cell Counting Kit-8 assay and colony formation assay. Wound healing and Transwell assays were used to analyze migration and invasion abilities, respectively, in OSCC cells. The luciferase reporter assay, RT-qPCR, and western blotting were used to determine the relationship between miR-99a-5p and isoprenylcysteine carboxylmethyltransferase (ICMT). Results miR-99a-5p expression in OSCC tissues and cell lines was significantly decreased compared with corresponding controls, and was significantly associated with clinical stage and lymph node metastasis in OSCC. Functional assays revealed that miR-99a-5p overexpression significantly inhibited the proliferation, migration, and invasion abilities of CAL-27 and TCA-8113 OSCC cells. miR-99a-5p was found to directly target ICMT, while ICMT restoration reversed the role of miR-99a-5p in OSCC cells. Conclusions Our results indicate that miR-99a-5p-mediates the down-regulation of ICMT, which could be used as a novel potential therapeutic target for OSCC treatment.

scholarly journals ID:2027 Deregulated expression of key components of phosphoinositide 3 kinase pathway in oral squamous cell carcinoma

2017 ◽  
Vol 4 (S) ◽  
pp. 59
Author(s):  
Satya N Das ◽  
Manasi Mittal ◽  
Manoj K Singh ◽  
Suresh C Sharma
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Pi3k Pathway ◽  
Strong Positive Correlation ◽  
Pi3k Inhibitors ◽  
Cancer Tissues

Oral squamous cell carcinoma (OSCC) is sixth common cancer in males globally. Deregulation of phosphatidylinositol-3-kinase (PI3K) pathway leads to various intracellular responses such as proliferation, survival, and inhibition of apoptosis. We evaluated the expression of key components of PI3K pathway in OSCC patients. RT-PCR and qRT-PCR was used asses the expression of different AKT isoforms, PTEN, TSC1 and TSC2 in tumor and normal tissues. The expression of various components of PI3K pathway e.g.Ser473pAKT, pan-AKT, PTEN and Ser2448pmTOR and mTOR was evaluated by western blot assay. Effect of selected PI3K inhibitors on OSCC cells (SCC-4, SCC-9 and SCC-25) was also studied. Approximately 1.4-fold higher expression of AKT1 and downregulation of AKT2 and AKT3 mRNA was observed in tumor tissue sections of patients as compared to controls. PTEN, TSC1 and TSC2 mRNA was found to be marginally decreases in tumor than the normal area. Significantly strong immunostaining of ser473p-AKT in comparison to AKT1 was documented in all paraffin fixed oral cancer tissues. Additionally, a strong positive correlation between the immuno-histochemical expression of AKT-1 and ser473p-AKT in the paraffin sections of oral cancer tissues was observed (r= 0.7504; p≤0.0001). Aberrant expression of key components of PI3K pathway was also found in OSCC cells that were reversed with the treatment of its inhibitors. Overall, our study suggests that PI3K pathway is deregulated OSCC patients and OSCC cell lines, with AKT1 being the predominantly expressed isoform. PI3K inhibitors restored such aberrations in OSCC cell lines.

scholarly journals TRPA1: A Potential Prognostic Indicator for Oral Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Rajdeep Chakraborty ◽  
Amara Jabeen ◽  
Honghua Hu ◽  
Charbel Darido ◽  
Karen Vickery ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cannabinoid Receptors ◽  
Prognostic Indicator ◽  
Oral Cancer Cells

Introduction: Transient receptors are related to oral cancer pain. Previously capsaicin (TRPV1 agonist) was shown to induce cell death in oral cancer cells. We hypothesised that these receptors are present in oral cancer. Method: We examined the presence of cannabinoid receptors (CB1 and CB2) and targets (TRPV1, TRPA1, CaV 3.1, CaV 3.2, CaV 3.3) via quantitative polymerase chain reaction (qPCR) in oral cancer cells SCC4, SCC9, SCC25, Cal27, and normal oral cell line OKF6. Result: Cannabinoid receptors are absent in all the cell lines, while TRPA1 is only present in normal cells, but absent in all the oral cancer cell lines. Voltage-gated calcium channels are present in all the cell lines. Conclusion and Future Aspects: TRPA1 could be the possible future prognostic indicator of oral squamous cell carcinoma. Future functionality assays could use precancerous cell lines to follow the loss of TRPA1.

scholarly journals Stem Cell Markers CXCR-4 and CD133 Predict Aggressive Phenotype and Their Double Positivity Indicates Poor Prognosis of Oral Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5895
Author(s):  
Ravindran Caspa Gokulan ◽  
Halagowder Devaraj
Keyword(s):  
Squamous Cell Carcinoma ◽  
Stem Cell ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Oral Cancer Cells

The activation of the SDF-1/CXCR-4 pathway is crucial for the invasion and metastasis of oral cancer cells. The CXCR-4 positive cells possess stem cell characteristics and express the cancer stem cell marker, CD133, in tumors of colon and pancreas. Despite several studies, the co-expression of CXCR-4 and CD133 and its significance is still largely unknown in oral cancer. Therefore, we aimed to investigate the impact of CXCR-4 and CD133 double positivity in the prognosis of oral cancer. The significance of PKC-δ, one of the key signaling molecules that regulates CXCR-4, was also analyzed. Immunohistochemistry and double immunofluorescence was used to investigate the co-localization of CXCR-4, PKC-δ and CD133 in the human tissues and cell lines of oral squamous cell carcinoma. The expression of CXCR-4, PKC-δ and CD133 were found to be higher in poorly differentiated and lymph node metastasis-positive cases. Interestingly, CXCR-4 positive cells showed positive staining for PKC-δ and CD133 in oral cancer tissue and cell lines. Moreover, CXCR-4+/CD133+ and CXCR-4+/PKC-δ+ double positive cases have the worst survival. We discovered, for the first time, that patients with expression of both CXCR-4 and CD133 have a lower survival rate, and CXCR-4+/CD133+, as well as CXCR-4+/PKC-δ+ double positivity, can be utilized to predict poor prognosis. CXCR-4, PKC-δ and CD133 might regulate aggressiveness and invasion of oral cancer cells.

A concerted cell and serum proteomic approach for the identification of oral squamous cell carcinoma biomarkers

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5512-5512
Author(s):  
A. M. Mlynarek ◽  
R. Balys ◽  
S. Jie ◽  
Y. Xu ◽  
M. P. Hier ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Serum Biomarkers ◽  
Mouse Serum ◽  
Proteomic Approach ◽  
Albumin Depletion

5512 Background: Head and neck squamous cell carcinoma is the sixth most common cause of cancer deaths in the world. Despite extensive research, the 5-year survival rates have not changed significantly over the last decade. Presently, the lack of serum biomarkers for head and neck carcinoma limits early diagnosis and treatment monitoring of advanced disease. In this study, we used a proteomic approach on serum from mice bearing human oral squamous cell carcinoma xenografts and from conditioned cell culture medium from matched cell lines. Methods: Oral squamous cell carcinomas, with distinct invasive phenotypes, and adjacent normal tissue were obtained from human patients, and were transplanted orthotopicaly into tongues of RAG-2/γ(c) mice. After a 20% weight loss, the mice were sacrificed by exsanguinations. Two distinct proteomic protocols were used to analyze the mouse serum. The first involved albumin depletion followed by two-dimensional gel electrophoresis and MALDI. The second arm utilized the same albumin depletion followed by multidimensional-protein-information-technology (ESI-LC and MS/MS). The top candidate proteins, which were differentially expressed in the cancer bearing mice compared to matched controls were then validated by Western blot, immunoprecipitation, immunofluorescence, and/or immunohistochemistry analyses using mouse serum and conditioned medium from matched cell lines. Results: Orthotopic implantation of human tumor tissues in mouse tongue was successful in 100% of the mice tested. The human origin of these tumors was confirmed pathologically. A correlation between disease stages and invasiveness was observed. We identified over one hundred proteins as being differentially expressed between control and cancer-bearing mice (p < 0.05), including proteins involved in cell cytoskeleton signaling. The expression of these proteins was then validated in mouse serum, tissue xenografts, and conditioned medium from oral cancer matched established cell lines. Conclusion: We report the first proteomic in-vivo model of oral cancer for the identification of low molecular weight serum biomarkers. We identified candidates that can be exploited as potential markers for diagnosis of human oral squamous cell carcinoma. No significant financial relationships to disclose.

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