• Title/Summary/Keyword: human oral squamous carcinoma cells

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Synthetic Chenodeoxycholic Acid Derivative HS-1200-Induced Apoptosis of Human Oral Squamous Carcinoma Cells (합성 Chenodeoxycholic Acid 유도체 HS-1200이 유도한 사람구강 편평상피암종세포 세포자멸사 연구)

  • Kim, In-Ryoung;Sohn, Hyeon-Jin;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo;Choi, Won-Chul;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.32 no.3
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    • pp.251-261
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    • 2007
  • Bile acids and synthetic its derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. Previous studies have been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis inducing activity on various cancer cells in vitro. It wasn't discovered those materials have apoptosis induced effects on YD9 human oral squamous carcinoma cells. The present study was done to examine the synthetic bile acid derivatives(HS-1199, HS-1200) induced apoptosis on YD9 cells and such these apoptosis events. We administered them in culture to YD9 cells. Tested YD9 cells showed several lines of apoptotic manifestation such as activation of caspase-3, degradation of DFF, production of poly (ADP-ribose) polymerase(PARP) cleavage(HS-1200 only), DNA degradation(HS-1200 only), nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential(HS-1200 only) and the release of cytochrome c and AIF to cytosol. Between two synthetic CDCA derivatives, HS-1200 showed stronger apoptosis-inducing effect than HS-1199. Therefore HS-1200 was demonstrated to have the most efficient antitumor effect. Taken collectively, we demonstrated that a synthetic CDCA derivative HS-1200 induced caspases-dependent apoptosis via mitochondrial pathway in human oral sqauamous carcinoma cells in vitro. Our data therefore provide the possibility that HS-1200 could be considered as a novel therapeutic strategy for human orall squamous carcinoma from its poweful apoptosis-inducing activity.

Tyrosine 1045 Codon Mutations in Exon 27 of EGFR are Infrequent in Oral Squamous Cell Carcinomas

  • Tushar, Mehta Dhaval;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4279-4282
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    • 2013
  • Background: The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far. Materials and Methods: Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed. Conclusions: The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.

Apoptotic effect of Pseudomonas aeruginosa exotoxin A in human tongue squamous cell carcinoma(SCC) 25 cells (Pseudomonas aeruginosa exotoxin A(PEA)가 사람혀 편평암종세포에서 나타나는 세포자멸사 작용)

  • Choi, Byul Bo-Ra;Kim, Gyoo-Cheon
    • Journal of Korean society of Dental Hygiene
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    • v.14 no.4
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    • pp.601-608
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    • 2014
  • Objectives : The purpose of the study is to examine the apoptotic effects of Pseudomonas aeruginosa exotoxin A(PEA) in squamous cell carcinoma(SCC) 25 cells. Methods : Cell growth reduction and apoptosis induced by PEA were confirmed by WST-1 assay, Hoechst 33258 staining, flow cytometry analysis, and Western blot assay. Results : The PEA treatment decreased the cell viability in a dose and time dependent manner: control; $100{\pm}0^e$(p<0.01), 0.1875 nM; $87{\pm}4.36^d$(p<0.01), 0.375 nM; $82{\pm}0.58^d$(p<0.01), 0.75 nM; $72{\pm}1.67^c$(p<0.01), 1.5 nM; $51{\pm}1.53^{bc}$(p<0.01), 7.5 nM; $31{\pm}1.20^{ab}$(p<0.01), 15 nM; $26{\pm}0.67^a$(p<0.01), control; $100{\pm}0^a$(p<0.05), 24 h; $51{\pm}1.53^b$(p<0.05), 48 h; $16{\pm}0.5^c$(p<0.05), 72 h; $12{\pm}1.67^d$%(p<0.05). The PEA was observed on SCC 25 cells with the half maximal inhibitory concentration(IC50) value of 1.5 nM at 24 hours. The PEA treated SCC 25 cells demonstrated several types of apoptotic indications, such as nuclear condensation, the increase of sub G1, and the cleavage of PARP-1 and DFF 45. Conclusions : PEA showed anti-cancer activity against SCC 25 cells via apoptosis. PEA may potentially contribute to human oral cancer treatment.

AN ATOPIC NUDE MOUSE MODEL OF ORAL CANCER CELL LINE (구강암 세포주의 이소위 누드마우스 종양 모델)

  • Kim, Jong-Hyun;Hwang, Young-Sun;Kim, Hyun-Sil;Nam, Woong;Cha, In-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.35 no.2
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    • pp.74-82
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    • 2009
  • In order to make successful oral cancer treatment, we need to understand about tumor biology and effective chemotherapeutic agents. To achieve these studies, it is necessary to develope a proper in-vivo model. Therefore the author will make try to develop more improved animal model of more applicable in various method of cancer study. In this study, the author induced in-vivo tumorigenesis in nude mice by $YD-10B_{mod}$ cell line used by YD-10B cell line originated from oral tongue squamous cell carcinoma and observed tumor formations and invasiveness of surrounding tissue, and found some results as follows : 1. The experimental group($YD-10B_{mod}$, subcutaneous injection) produced tumors 13 out of 15 mice, while the control group produced none of 5 mice. 2. The inoculation of $1{\times}10^6$cells/mouse produced tumors 3 out of 5 mice and inoculation of $1{\times}10^7$cells/mouse, $2{\times}10^7$cells/mouse produced tumors in every 5 mice. 3. In the histopathologic studies, the inoculation of $1{\times}10^6$cells/mouse group showed the characteristic features of well-differentiated squamous cell carcinoma and demarcated expansile growth, while the inoculation of $1{\times}10^7$cells/mouse, $2{\times}10^7$cells/mouse group showed the expansile growth with partial central necrosis and invasive growth to surrounding fat & connective tissue. These findings suggest that atopic xenograft of $YD-10B_{mod}$ cell line in nude mice has a improved productivity of tumors, produced tumors showed the characteristics feature of human tumor and invasive growth to surrounding tissue in histopathologic appearance. These atopic nude mouse model of tongue carcinoma might assist in studying oral cancer biology and effective choice of chemotherapeutic agents.

Pseudomonas aeruginosa Exotoxin A Induces Apoptosis in Chemoresistant YD-9 Human Oral Squamous Carcinoma Cell Line Via Accumulation of p53 and Activation of Caspases (항암제에 저항성을 가지는 YD-9 human oral squamous carcinoma cell line에서 Pseudomonas aeruginosa exotoxin A의 p53 단백질 누적과 caspase를 활성화 경로를 통해 유도된 세포자멸사)

  • Kim, Gyoo-Cheon;Gil, Young-Gi
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1047-1054
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    • 2009
  • Oral squamous carcinoma (OSC) cells present resistance to chemotherapeutic agents-mediated apoptosis in the late stages of malignancy. Advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers. It was demonstrated here that Pseudomonas aeruginosa exotoxin A (PEA) significantly decreased the viability of chemoresistant YD-9 cells in the apoptosis mechanism. Apoptotic manifestations were evident through changes in nuclear morphology and generation of DNA fragmentation. PEA treatment induced caspase-3, -6 and -9 cleavage, and activation. These events preceded proteolysis of the caspase substrates poly (ADP-ribose) polymerase (PARP), DNA fragmentation factor 45 (DFF45), and lamin A in YD-9 cells. The reduction of mitochondrial membrane potential, release of cytochrome c and SmacjDlABLO from mitochondria to cytosol, andtranslocation of AlF into nucleus were shown. While p53, p21 and $14-3-3{\gamma}$ were upregulated, cyclin Band cdc2 were downregulated by PEA treatment. Taken together, PEA induces apoptosis in chemoresistant YD-9 cells via activation of caspases, mitochondrial events and regulation of cell cycle genes.

Effect of autophagy in human tongue squamous cell carcinoma SCC 25 cells from Scutellariae Radix by ethanol extract (에탄올에 의해 추출한 황금이 구강암 세포에서 나타나는 자가포식작용)

  • Choi, Byul Bo-Ra
    • Journal of Korean society of Dental Hygiene
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    • v.14 no.2
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    • pp.287-292
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    • 2014
  • Objectives : The purpose of the study is to examine the cell growth effect and autophagy effect of Scutellariae Radix by ethanol extract in SCC 25 cells. Methods : Cell growth inhibitory effect and autophagy induced by Scutellariae Radix were confirmed by WST-1 assay, monodansylcadaverine(MDC) stain, and flow cytometry by acridine orange(AO) stain. Results : The Scutellariae Radix treatment decreased the cell proliferation in a dose and time dependent manner. Scutellariae Radix has anticancer effects that autophagic vacuoles were apparent by MDC and AO staining in SCC 25 cells. Conclusions : Scutellariae Radix showed anticancer activity against SCC 25 cells via autophagy. The data provided the possibility that Scutellariae Radix may potentially contribute to oral cancer treatment.

EXPRESSION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND CELL CYCLE ANALYSIS IN THE HEAD AND NECK SQUAMOUS CELL CARCINOMAS (두경부 편평세포암종에서 상피성장인자수용체의 발현과 세포주기에 관한 연구)

  • Kim, Kyoung-Won;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.2
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    • pp.154-163
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    • 2000
  • Growth factors and the receptors play an important role in the regulation of the growth and development of mammalian cells. In particular, epidermal growth factor is a polypeptide with potent mitogenic activity that stimulates proliferation of various normal and neoplastic cells through the interaction with its specific receptor(EGFR). EGFR has been described as a parameter of poor prognosis in many human neoplasms such as breast, bladder, and vulvar cancers. The objectives of this study are the evaluation of the expression of EGFR and cell cycle analysis in the head and neck squamous cell carcinomas(SCC), and the evaluation of the correlation between clinico-patholgic features and expression of EGFR and S-phase fraction. 37 head and neck squamous cell carcinoma specimens were evaluated for expression of EGFR by Western blot analysis and S-phase fraction by cell cycle analysis using the flow cytometry. The obtained results were as follows : 1. The expressions of EGFR were observed in 20 specimens(54%) among 37 head and neck SCC specimens. In case of oral SCC, 15 specimens(56%) out of 27 specimens were observed, and in case of nasopharyngeal SCC 5 specimens(50%) out of 10 specimens. 2. There was no correlation between clinical features(location, stage) of head and neck SCC and expression of EGFR (p>0.05). 3. There was a significant correlation between histo-pathological differentiation of head and neck SCC and expression of EGFR (p<0.02). 4. There was a significant correlation between expression of EGFR and S-phase fraction of cell cycle in the head and neck SCC (p<0.05). The above results suggest that expression of EGFR and S-phase fraction of cell cycle are adjunctive prognostic marker in the head and neck squamous cell carcinomas.

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Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

  • Satpute, Pranali Shirish;Hazarey, Vinay;Ahmed, Riyaz;Yadav, Lalita
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5579-5587
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    • 2013
  • Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the "drivers" of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

COMPARATIVE IMMUNOHISTOCHEMICAL ASSAYS FOR THE EXPRESSION OF ANGIOGENIC FACTORS IN TUMORS OF HUMAN SALIVARY GLANDS (타액선 종양에서 혈관형성 인자의 발현에 관한 면역조직화학적 비교 연구)

  • In, Yeon-Soo;Kim, Soung-Min;Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.29 no.1
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    • pp.10-23
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    • 2007
  • Hallmarks of clinical behaviors of adenoid cystic carcinoma(ACC) of salivary glands are the delayed onset of vascular metastasis and poor responses to classical chemotherapeutic agents. Poor prognoses from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, cellular and molecular characteristics that influence the dissemination of metastatic cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of angiogenic proteins in benign (pleomorphic adenoma) and malignant (ACC, mucoepidermoid carcinoma) tumors of salivary glands and compared each other and to those in oral squamous cell carcinoma. Using surgical specimens, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), phosphorylated VEGFR-2 (pVEGFR-2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. Most angiogenic factors were overexpressed in malignant salivary tumors than in pleomorphic adenoma which is benign nature. Moreover, ACC demonstrated more expression of VEGFR-2 than that of squamous cell carcinoma which used as control. Conclusively, these data show those angiogenic factors produced by salivary gland tumors may affect the propagation and metastasis of malignant cells of salivary tumors, and could be used as biomarkers for the malignant transformation of salivary gland tumors. Prospectively, although further studies will be needed, these biomarkers related to angiogenesis can be molecular targets for the therapy of salivary ACC, which has propensity for delayed vascular metastasis.

An orthotopic nude mouse model of tongue carcinoma (구강암 세포주를 이종이식한 설암의 동소위 누드마우스 모델)

  • Chung, Jae-Seung;Kim, So-Mi;Hwang, Young-Sun;Zhang, Xianlan;Cha, In-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.37 no.6
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    • pp.490-495
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    • 2011
  • Introduction: Development of carcinoma on oral tongue may cause bilateral cervical lymph node metastasis, rapid invasion and growth of the cancer cells due to rich blood supply in muscle tissues. It is not only difficult to develop an animal experimental model, but also to proceed follow-up research after the development of such model as the induction of cancer lead to difficulty in taking nutrition for the experimental animals that often causes early death. Materials and Methods: IIn this study, author have transplanted YD-$10B_{mod}$ cells into nude mouse oral tongues with different cells number ($5{\times}10^4$, $5{\times}10^5$, $5{\times}10^6$ cells/mouse) and observed the development aspect of oral tongue cancers. Results: The cancer developed from orthotopic transplantation of YD-$10B_{mod}$ cells into nude mouse oral tongue show invasion and central necrosis of the tumor, similar to the cancers developed human oral tongue cancer. The difference in tumor size and the time of central necrosis development depending on the number of transplanted tumor cells shows the feasibility of extending the survival period of the nude mouse by limiting the transplanted tumor cells to < $5{\times}10^4$ cells/mouse or under per nude mouse. Conclusion: This nude mouse model could be used effectively in developing effective chemotheray agent and establishing an animal experimental model that can be used to study the mechanism of cervical lymph node metastasis of the oral tongue cancer.