• Genomics & Informatics
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• v.10 no.1
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• pp.23-32
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• 2012

There are lots of studies attempting to identify the expression changes in oral squamous cell carcinoma. Most studies include insufficient samples to apply statistical methods for detecting significant gene sets. This study combined two small microarray datasets from a public database and identified significant genes associated with the progress of oral squamous cell carcinoma. There were different expression scales between the two datasets, even though these datasets were generated under the same platforms - Affymetrix U133A gene chips. We discretized gene expressions of the two datasets by adjusting the differences between the datasets for detecting the more reliable information. From the combination of the two datasets, we detected 51 significant genes that were upregulated in oral squamous cell carcinoma. Most of them were published in previous studies as cancer-related genes. From these selected genes, significant genetic pathways associated with expression changes were identified. By combining several datasets from the public database, sufficient samples can be obtained for detecting reliable information. Most of the selected genes were known as cancer-related genes, including oral squamous cell carcinoma. Several unknown genes can be biologically evaluated in further studies.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.273-280
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• 2007

New treatment approaches are needed to improve the effectiveness of oral cancer treatment, since surgical resection of the tumor in oral region causes various oral dysfunctions. The molecular biology of oral cancer has been progressively delineated. Concurrently, gene therapy techniques have been developed that allow targeting or replacement of dysfunctional genes in cancer cells, offering the potential to treat a wide range of cancer. Oral carcinoma is attractive target for gene therapy because of its accessibility. In this article, we review the current status of gene therapy as applied to oral carcinoma.

• International Journal of Oral Biology
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• v.41 no.4
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• pp.183-190
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• 2016

Anthricin (Deoxypodophyllotoxin), a naturally occurring flavolignan, has well known anti-cancer properties in several cancer cells, such as prostate cancer, cervical carcinoma and pancreatic cancer. However, the effects of Anthricin are currently unknown in oral cancer. We examined the anticancer effect and mechanism of action of Anthricin in human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that Anthricin inhibits cell viability in a dose- and time-dependent manner ($IC_{50}$ 50 nM) in the MTT assay and Live & Dead assay. In addition, Anthricin treated FaDu cells showed marked apoptosis by DAPI stain and FACS. Furthermore, Anthricin activates anti-apoptotic factors such as caspase-3, -9 and poly (ADP-ribose) polymerase (PARP), suggesting that caspase-mediated pathways are involved in Anthricin- induced apoptosis. Anthricin treatment also leads to accumulation of the pro-apoptotic factor Bax, followed by inhibition of cell growth. Taken together, these results indicate that Anthricn-induced cell death of human FaDu hypopharyngeal squamous carcinoma cells is mediated by mitochondrial-dependent apoptotic pathway. In summary, our findings provide a framework for further exploration on Anthricin as a novel chemotherapeutic drug for human oral cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.1-10
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• 2008

Oral squamous cell carcinoma (OSCC) is the most frequent form of oral cancer and holds the eighth position in the cancer incidence ranking. OSCC patients are treated by classical therapeutic modalities consisting of surgery, radiotherapy, and/or chemotherapy. But OSCC still shows significant mortality rates. Thus, new therapeutic approaches have been investigated and the most promising one is naturally acquired agents with known anti-cancer effects. Genistein is a compound extracted from soy bean. Its anti-cancer effect on breast cancer is well established now and it is investigated whether it has similar effect on OSCC. It inhibited the growth and invasive-ness of OSCC cells in vitro, but these effects did not work in living animals in vivo. Catechin is a compound from green tea and its anti-cancer effect on OSCC is known better than other agents. Catechin showed its anti-cancer effect in vitro via induction of apoptosis, cell cycle arrest, inhibition of growth, and down-regulation of invasion/metastasis. These effects were confirmed in vivo with mouse model. Cordycepin is one of major pharmacologically important components in Cordyceps Militaris and may exert its anti-cancer effect as an adenosine receptor agonist. In recent study, it inhibited the proliferation of OSCC cells via A3 adenosine receptor. But because there is very scarce evidence on this effect, more researches are needed on this theme.

• International Journal of Oral Biology
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• v.32 no.3
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• pp.93-101
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• 2007

Cell behavior of the transformed cells is known to affect by interaction with extracellular matrix (ECM) proteins and integrin. To investigate the alterations of both integrin expression and cell-matrix interaction during neoplastic conversion of human oral kerationcytes, we studied expression levels of integrin subunits by flow cytometry and cellular responses to the ECM proteins in normal human oral keratinocytes (NHOKs), HPV-immortalized HOK-16B line, and three oral cancer cell lines established from HOK-16B line, CTHOK-16B-BaP, CTHOK-16B-DMBA, and CTHOK-16B-Dexa lines. The expression levels of ${\alpha}\;and\;{\beta}$ integrin subunits were shown decreased tendency in human oral keratinocytes undergoing immortalization and tumorigenic transformation except CTHOK-16B-DMBA line tested. Although ${\alpha}v{\beta}6$ integrin is known to be highly expressed in squamous cell carcinomas, and the altered integrin expression is suspected to be associated with cellular carcinogenesis, ${\alpha}v$ integrin subunit and ${\alpha}v{\beta}6$ integrin did not express in oral cancer cell lines tested. Cell behavior to the ECM proteins in HOK-16B line was generally similar to that of exponentially proliferating NHOKs. The adhesion activity profiles of type I collagen were very similar to that of its laminin counterparts, but fibronectin showed minimal adhesion activity under our conditions compared to the BSA control. The ability of the CTHOK-16B-BaP line to spread upon type I collagen and laminin markedly decreased, but migration was notably increased on type I collagen. In contrast, CTHOK-16B-DMBA and CTHOK-16B-Dexa lines spread less but migrated more upon type I collagen than immortalized HOK-16B line. These data indicate that downregulation of integrin subunits causes the changes of cellular responses to the ECM proteins during neoplastic conversion of human oral keratinocytes, and that cellular responses to the ECM proteins in oral cancer cell lines established by exposing different carcinogens are variable according to chemical carcinogens treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1599-1603
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• 2015

Background: Epigenetic silencing of tumor suppressor genes due to promoter hypermethylation is one of the frequent mechanisms observed in cancers. Hypermethylation of several tumor suppressor genes involved in cell cycle regulation has been reported in many types of tumors including oral squamous cell carcinomas. LATS1 (Large Tumor Suppressor, isoform 1) is a novel tumor suppressor gene that regulates cell cycle progression by forming complexes with the cyclin dependent kinase, CDK1. Promoter hypermethylation of the LATS1 gene has been observed in several carcinomas and also has been linked with prognosis. However, the methylation status of LATS1 in oral squamous cell carcinomas is not known. As oral cancer is one of the most prevalent forms of cancer in India, the present study was designed to investigate the methylation status of LATS1 promoter and associate it with histopathological findings in order to determine any associations of the genetic status with stage of differentiation. Materials and Methods: Tumor chromosomal DNA isolated from biopsy tissues of thirteen oral squamous cell carcinoma biopsy tissues were subjected to digestion with methylation sensitive HpaII enzyme followed by amplification with primers flanking CCGG motifs in promoter region of LATS1 gene. The PCR amplicons were subsequently subjected to agarose gel electrophoresis along with undigested amplification control. Results: HpaII enzyme based methylation sensitive PCR identified LATS1 promoter hypermethylation in seven out of thirteen oral squamous cell carcinoma samples. Conclusions: The identification of LATS1 promoter hypermethylation in seven oral squamous cell carcinoma samples (54%), which included one sample with epithelial dysplasia, two early invasive and one moderately differentiated lesions indicates that the hypermethylation of this gene may be one of the early event during carcinogenesis. To the best of our knowledge, this is the first study to have explored and identified positive association between LATS1 promoter hypermethylation with histopathological features in oral squamous cell carcinomas.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.6
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• pp.474-481
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• 2004

Squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its low survival rate, high malignancy, mortality with facial defects, and poor prognosis. Exact cause and pathogenesis of the squamous cell carcinoma is still unknown. Various routes including smoking, radiation, and viral infections predispose its genesis, and recent studies revealed that genetic defects which fail to prevent cancer proliferation play a role. Generally, a cancer develops from the decreased rate of apoptosis which is an active and voluntary cell death, and from the altered cell cycles. Anticancer effect can be obtained by recovering the apoptotic process, and by suppressing the cell cycles. Among the apoptosis related factors, bcl-2, caspase-9, and VDAC (voltage-dependent anion channel)are produced in mitochondria of the cell. Cyclosporin-A is known to induce apoptosis through its activation with VDAC. This study was to reveal the anticancer effect of Cyclosporin A to the oral squamous cell carcinoma. The inverted microscope was used to find alterations in the tissue, and sensitivity test to the anticancer cells was performed with MTT (Tetrazolium-based colorimetric) assay. Following cell line culture of primary and metastastic oral squamous cell carcinoma, electrophoresis was performed with extracted total RNA. Finally, semi-quantitative study was carried out through RT-PCR (Reverse Transcription-Polymerase Chain Reaction). The results of this study are as follows: 1. The inverted microscopic observation revealed a poorly defined cytoplasm at $2000ng{\sim}3000ng/ml$, indistinct nucleus, and apoptosis. 2. The Growth of cancer cells was decreased at 1000ng/ml of cyclosporin-A. No cancer cell growth was observed at over 2000ng/ml concentration of cyclosporin-A, and at one week, growth of cancer cells was ceased. 3. The MTT assays were decreased as cyclosporin-A concentration was increased. This means that the activation of succinyl dehydrogenase in mitochondria was decreased following administration of cyclosporin A. 4. A result of RT-PCR showed that amount of mRNA of VDAC-2 was decreased half times at a cyclosporine-A concentration of 2000ng/ml. In bcl-2, amount of mRNA was significantly decreased 1/5 times at 2000ng/ml. caspase-9, however, showed slight increase compared to the control group. From the results obtained in this study, administration of cyclosporin-A to the cell lines of oral squamous cell carcinoma induced alterations in morphology and growth of the cells as its concentration increased. Since apoptosis related factors such as VDAS-2, bcl-2, and caspase-9 also showed distinct alterations on their mRNAs, further research on cyclosporin A as an anti-cancer agent will be feasible.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1891-1898
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• 2016

Imperata cylindrica, a tall tufted grass which has multiple pharmacological applications is one of the key ingredients in various traditional medicinal formula used in India. Previous reports have shown that I. cylindrica plant extract inhibited cell proliferation and induced apoptosis in various cancer cell lines. To our knowledge, no studies have been published on the effect of I. cylindrica leaf extract on human oral cancers. The present study was undertaken in order to evaluate the anticancer properties of the leaf extract of I. cylindrica using an oral squamous cell carcinoma cell line SCC-9 as an in vitro model system. A methanol extract from dried leaves of I. cylindrica (ICL) was prepared by standard procedures. Effects of the ICL extract on the morphology of SCC-9 cells was visualized by microscopy. Cytotoxicity was determined by MTT assay. Effects of the ICL extract on colony forming ability of SCC-9 cells was evaluated using clonogenic assay. Cell cycle analysis was performed by flow cytometry and induction of apoptosis was determined by DNA fragmentation assay. The ICL extract treatment caused cytotoxicity and induced cell death in vitro in SCC-9 cells in a dose-dependent manner. This treatment also significantly reduced the clonogenic potential and inhibited cell proliferation by arresting the cell cycle in the G2/M phase. Furthermore, DNA fragmentation assays showed that the observed cell death was caused by apoptosis. This is the first report showing the anticancer activity of the methanol extracts from the leaves of I. cylindrica in human oral cancer cell line. Our data indicates that ICL extract could be considered as one of the lead compounds for the formulation of anticancer therapeutic agents to treat/manage human oral cancers. The natural abundance of I. cylindrica and its wide geographic distribution could render it one of the primary resource materials for preparation of anticancer therapeutic agents.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5243-5245
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• 2016

Background and Objective : Bone morphogenic protein-2 (BMP-2) plays an essential role in mesenchymal cell differentiation into osteoblasts، through many intracellular pathways which may also be active in tumors. Invasive oral squamous cell carcinomas account for more than 90% of head and neck malignancies in many cancer registries. They are classified into three types according to epithelial cell differentiation. The present study aimed to identify any relation between BMP-2 expression and tumor histology. Materials and methods: BMP-2 expression was compared immunohistochemically among 30 cases (19 male and 11 female, mean age 48 years) of oral squamous cell carcinoma, Division was into 3 groups (each containing 10 cases) according to the histological grade. Results: No significant correlation between BMP-2 expression and histological grade was observed. Changes in localization and cytoplasmic staining were also not apparent. Conclusion: From the results of this study BMP-2 does not appear to have any application as a prognostic marker for oral squamous cell carcinomas.

• International Journal of Oral Biology
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• v.32 no.3
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• pp.113-118
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• 2007

Treatment of oral cancers with chemotherapeutic agents become evaluated as an effective method to reduce cancer cell proliferation. Anti-proliferative and anti-oral cancer activities of momordin I on oral cancer cells were evaluated in this study. Momordin I was originally purified from a natural product, Ampelopsis radix and showed the antiproliferative activity against oral carcinoma, KB cells. Obtained $IC_{50}$ value was approximately $10.4{\mu}g/ml$. Time-and dose-dependent chromosomal DNA fragmentations were observed in momordin I-treated KB cells. Flow cytometry analysis showed time-dependent apoptotic cell appearance after treatment of momordin I. Approximately 18.6% apoptotic cells were observed at 72 hours after $20{\mu}g/ml$ of momordin I treatment. These observation were consistent with the results obtained in DNA fragmentation analysis. These data suggest that momordin I has anti-proliferative effect and induces cell death in KB cells through apoptosis.