scholarly journals Tongue Cancer and Epigenetic Factors: An in-vitro Study on 298 Micro-RNAS

2012 ◽  
Vol 10 (3) ◽  
pp. 447-454
Author(s):  
A. Guida ◽  
G. Pannone ◽  
A. Lucchese ◽  
R. Serpico ◽  
D. Pasquali ◽  
...  

Oral Squamous Cell Carcinoma (OSCC) is the sixth most frequent malignant tumour. There is some evidence that tongue cancer has a higher local failure rate and poorer prognosis than other anatomical sites in the oral cavity. We used tongue squamous cell carcinoma cell lines harbouring mutated p53/p16 as tongue cancer models to study the influences exerted by p53 and p16 genes on the expression of micro RNAs (miRNAs). The study was performed on microarray chips harbouring 298 miRNA sequences. OSCC cell lines used in this study were SCC-4, SCC-15 and SCC-25, all three carrying mutated/hypermethylated p53/p16. The expression values normalized to healthy control of 298 miRNAs were obtained for each cell line. MiRNA 196b was found hyperexpressed in the three cell lines. MiRNAs 19b-1, 21, 27a, 30d, 134, 339, 379 and 465 were found altered in two out of three cell lines. miRNAs found altered in one cell line out of three were: 7b, 23a, 25, 30c, 30e-3p, 107,125b, 124a, 214, 216, 325 and 384. A literature review for each miRNA found significant was undertaken. Some miRNAs have a well-known role in oral cancer, some have been put in correlation with other cancers/diseases, others are found significant for the first time. These early results in tongue cancer cell lines harbouring mutation of p16/p53 need further analyses to understand whether this variation of miRNA levels are directly influenced by the malfunction of these proteins or if, vice-versa, altered miRNA levels influence the function of p16 and p53.

Author(s):  
Zhigeng Zou ◽  
Wei Zheng ◽  
Hongjun Fan ◽  
Guodong Deng ◽  
Shih-Hsin Lu ◽  
...  

Abstract Background Cancer stem cells (CSCs) are related to the patient’s prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood. Methods We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells. Results ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model. Conclusions ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Antonio Celentano ◽  
Callisthenis Yiannis ◽  
Rita Paolini ◽  
Pangzhen Zhang ◽  
Camile S. Farah ◽  
...  

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.


2019 ◽  
Vol 20 (14) ◽  
pp. 3428 ◽  
Author(s):  
Sakinah Hassan ◽  
Karin J. Purdie ◽  
Jun Wang ◽  
Catherine A. Harwood ◽  
Charlotte M. Proby ◽  
...  

Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to rise with increasing morbidity and mortality, with limited treatment options for advanced disease. Future improvements in targeted therapy will rely on advances in genomic/transcriptomic understanding and the use of model systems for basic research. We describe here the panel of 16 primary and metastatic cSCC cell lines developed and characterised over the past three decades in our laboratory in order to provide such a resource for future preclinical research and drug screening. Methods: Primary keratinocytes were isolated from cSCC tumours and metastases, and cell lines were established. These were characterised using short tandem repeat (STR) profiling and genotyped by whole exome sequencing. Multiple in vitro assays were performed to document their morphology, growth characteristics, migration and invasion characteristics, and in vivo xenograft growth. Results: STR profiles of the cSCC lines allow the confirmation of their unique identity. Phylogenetic trees derived from exome sequence analysis of the matched primary and metastatic lines provide insight into the genetic basis of disease progression. The results of in vivo and in vitro analyses allow researchers to select suitable cell lines for specific experimentation. Conclusions: There are few well-characterised cSCC lines available for widespread preclinical experimentation and drug screening. The described cSCC cell line panel provides a critical tool for in vitro and in vivo experimentation.


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