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

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Lipopeptides Extract from Bacillus Amyloliquefaciens Induce Human Oral Squamous Cancer Cell Death

  • Kuo, Chen-Hui;Lin, Yun-Wei;Chen, Ruey-Shyang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.91-96
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    • 2015
  • A lipopeptide extract of Bacillus amyloliquefaciens BACY1 (BLE) was found to induce cell death in human oral squamous cell carcinoma (OSCC) cell lines, SCC4 and SCC25, in this study. The results of MTT assay showed that BLE inhibited OSCC cell proliferation in a dose-dependent manner. BLE was also effective in increasing the sub-G1 phases. Furthermore, when membrane damage in SCC4 cells treated with BLE was monitored by LDH assay, release of LDH was significantly increased. The protein and mRNA levels of pro-apoptotic Bax, and caspase-3 were up-regulated by BLE. Taken together, these results suggest that BLE induces apoptosis and then inhibits the cell proliferation of human OSCC cells.

Methanol Extracts of Codium fragile Induces Apoptosis through G1/S Cell Cycle Arrest in FaDu Human Hypopharynx Squamous Carcinoma Cells

  • Lee, Seul Ah;Park, Bo-Ram;Moon, Sung Min;Kim, Do Kyung;Kim, Chun Sung
    • International Journal of Oral Biology
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    • v.43 no.2
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    • pp.61-68
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    • 2018
  • Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

Coptidis Rhizoma Extract induces Apoptotic Cell Death in YD-10B Cell (황련(黃連)이 구강암 세포에서의 세포자멸사에 미치는 영향)

  • Lee, Jae-Geun;Park, Sook-Jahr;Kim, Sang-Chan;Jee, Seon-Young
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.2
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    • pp.50-59
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    • 2009
  • Objectives : The aim of this study was conducted that CRE (Coptidis Rhizoma Extract) induces apoptosis in YD-10B cells, human oral squamous carcinoma cell line. Methods : In this study, YD-10B cells were exposed to CRE (0.03-0.30 mg/ml), for 6-24 hours. We measured the effects of CRE on the changes of cell viability and cell membrane, TUNEL assay of CRE-treated YD-10B cell. Results : In this study, CRE caused a decrease of viability in YD-10B cells, human oral squamous carcinoma cell line. When YD-10B cells were treated with CRE, cells showed dose-dependent manner apoptotic cell death. Conclusions : These results suggest that CRE may be potential therapeutic approach in the clinical management of oral squamous cell carcinoma.

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Trifolium pratense induces apoptosis through caspase pathway in FaDu human hypopharynx squamous carcinoma cells

  • Lee, Seul Ah;Park, Bo-Ram;Kim, Chun Sung
    • International Journal of Oral Biology
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    • v.44 no.3
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    • pp.81-88
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    • 2019
  • Trifolium pratense leaves (red clover) has been used in Oriental and European folk medicine for the treatment of whooping cough, asthma, and eczema, and is now being used to treat and alleviate the symptoms, such as hot flushes, cardiovascular health effects that occur in postmenopausal women. However, relatively little scientific data is available on the physiological activity of this plant. Therefore, in this study, we investigated the anti-cancer activity of T. pratense leaves using methanol extract of T. pratense leaves (MeTP) on human FaDu hypopharyngeal squamous carcinoma cells. MeTP inhibited the viability of FaDu cells by inducing apoptosis through the cleavage of procaspase-3, -7, and -9 and poly (adenosine diphosphate ribose-ribose) polymerase (PARP), downregulation of Bcl-2, and upregulation of Bax, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Live & dead assay, 4'6-diamidino-2-phenylindole stain, fluorescence-activated cell sorting analysis, and Western blot analysis. In addition, colony formation was slightly inhibited when FaDu cells were treated with a non-cytotoxic concentration (0.125 mg/mL) of MeTP and almost completely inhibited when cells were treated with 0.25 mg/mL MeTP. Collectively, these results indicate that MeTP induced cell apoptosis via caspase- and mitochondrial-dependent apoptotic pathways, and inhibited colony formation of cancer cells in FaDu human hypopharyngeal squamous carcinoma cells. These findings suggest MeTP should be considered for clinical development as a chemotherapeutic option in oral cancer.

BONE METASTASIS MODEL OF ORAL SQUAMOUS CELL CARCINOMA (구강 편평상피세포암의 골전이 모델)

  • Park, Young-Wook;Oh, Yu-Jin;Lee, Hee-Su
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.2
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    • pp.118-125
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    • 2010
  • Background and Purpose: Bone metastases rarely occur in patients with oral squamous cell carcinoma (OSCC), so the molecular mechanisms of bone metastasis of OSCC remains unclear. Studies with animal models allow progresses in understanding the molecular events for bone metastasis and provide new targets for therapy. So we tried to establish a murine model for bone metastasis of oral squamous cell carcinoma. Materials and Methods: Human OSCC cells (KB cell line) were xenografted to nude mice via direct inoculation into the tibial marrow. Mice with tibial tumors were sacrificed once a week, until seven weeks after the injection of human tumor cells. Growth of tibial tumors were observed by histology. Expression of TGF-$\beta$ and CXCR-4 in bone OSCC (experimental) and subcutaneous tumor (control) was also evaluated by immunohistochemical staining. Results: Bone OSCC was successfully induced by intra-tibial injection of KB cells. Tumor mass was developed in the marrow tissues of tibia and finally invade the endosteum of tibia. Immunohistochemical staining showed higher expression of TGF-$\beta$ in bone tumors than in subcutaneous tumors. Conclusion: A murine model of bone metastasis of OSCC was suggested that imitated the clinical findings of distant vascular metastasis. This bone tumor model should facilitate understanding of the molecular pathogenesis of OSCC bone metastasis, and aid in the developement of treatment strategies against OSCC bone metastasis.

Inhibition of cell growth and induction of apoptosis by bilobalide in FaDu human pharyngeal squamous cell carcinoma

  • Jeong, Kyung In;Kim, Su-Gwan;Go, Dae-San;Kim, Do Kyungm
    • International Journal of Oral Biology
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    • v.45 no.1
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    • pp.8-14
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    • 2020
  • Bilobalide isolated from the leaves of Ginkgo biloba has several pharmacological activities such as neuroprotective, anti-inflammatory, and anticonvulsant. However, the effect of bilobalide on cancer has not been clearly established. The main purpose of this study was to investigate the effect of bilobalide on cell growth and apoptosis induction in FaDu human pharyngeal squamous cell carcinoma. This was examined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, nuclear 4′,6-diamidino-2-phenylindole dihydrochloride staining, DNA fragmentation analysis, and immunoblotting. Bilobalide inhibited the growth of FaDu cells in dose- and time-dependent manners. Treatment with bilobalide resulted in nuclear condensation and DNA fragmentation in FaDu cells. Furthermore, it promoted the proteolytic cleavage of procaspase-3/-7/-8/-9 with increase in the amount of cleaved caspase-3/-7/-8/-9. Bilobalide-induced apoptosis in FaDu cells was mediated by the expression of Fas and the activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting revealed that the antiapoptotic mitochondrial protein Bcl-2 was downregulated, but the proapoptotic protein Bax was upregulated by bilobalide in FaDu cells. Bilobalide significantly increased Bax/Bcl-2 ratio. These results suggest that bilobalide inhibits cell proliferation and induces apoptosis in FaDu human pharyngeal squamous cell carcinoma via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondrial-mediated intrinsic apoptotic pathway.

Comparative Expression of Bcl-2 and NOS2 in Oral White Lesions and Squamous Cell Carcinoma (구강내 백색병소와 편평상피세포암종에서 bcl-2와 NOS2 비교발현에 관한 연구)

  • Shin, Min;Kim, Eun-Cheol
    • Journal of Oral Medicine and Pain
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    • v.24 no.2
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    • pp.145-161
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    • 1999
  • The proto-oncogene bcl-2 confers a survival advantage to cells by blocking programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been observed in human colon cancer cell lines as well as in human gynecological, breast, and CNS tumors. However there have been only a few reports on the expression of bcl-2 and $NOS_2$ in oral white lesions and cancer. The aim of this study was to investigate the relationship between the expression of Bcl-2 and $NOS_2$ and several pathological parameters such as histological types and layers. We reported desregulation of bcl-2 and $NOS_2$ expression during progression from oral white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained results were as follows: 1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and $NOS_2$ in formalin-fixed paraffin-embedded tissue sections revealed that bcl-2 expression is restricted to the basal cell layer and $NOS_2$ was mild expressed only in subepithelial inflammatory cells in normal human mucosa. There wasn't specific finding of those in lichen planus and leukoplakia. 2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, $NOS_2$ reactivity in most superficial layer were noted. 3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In moderated and poor squamous cell carcinomas, the expression of $NOS_2$ was increased and that of bcl-2 was decreased. 4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44% of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50% and 67% according to differentiation, respectively. 5. The immunoreactivity of $NOS_2$ was 25% of normal mucosa, 70% of leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated type(71%). 6. The expression of bcl-2 and $NOS_2$ by Western blot was increased highly in lichen planus and leukoplakia. Therefore, the expression of bcl-2 was increased in the white and precancerous lesions and that was decreased by differentiation of carcinoma. However, $NOS_2$ immunoreactivity in carcinoma in situ was lower than those in moderated and poor squamous cell. These findings suggest that the interaction of bcl-2 and $NOS_2$ may be roled importantly in growth and development of carcinoma.

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EXPRESSIONS OF METASTASIS-RELATED FACTORS IN ORTHOTOPIC TUMOR MODELS OF ORAL SQUAMOUS CELL CARCINOMA (구강 편평상피세포암 동위종양 모델에서 전이관련 인자의 발현)

  • Park, Young-Wook;Lee, Jong-Won;Kim, So-Hee
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.6
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    • pp.529-539
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    • 2008
  • Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

CONCOMITANT INHIBITION OF EPIDERMAL GROWTH FACTOR AND VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR TYROSINE KINASES IN ORAL SQUAMOUS CELL CARCINOMA (구강 편평상피세포암에서 상피성장인자 수용체와 혈관내피성장인자 수용체 타이로신 활성화효소의 동시 억제)

  • Park, Young-Wook;Lee, Sang-Shin
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.3
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    • pp.193-201
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    • 2006
  • Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

14-3-3ζ Regulates Immune Response through Stat3 Signaling in Oral Squamous Cell Carcinoma

  • Han, Xinguang;Han, Yongfu;Jiao, Huifeng;Jie, Yaqiong
    • Molecules and Cells
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    • v.38 no.2
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    • pp.112-121
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    • 2015
  • Ectopic expression of $14-3-3{\zeta}$ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of $14-3-3{\zeta}$ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how $14-3-3{\zeta}$ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that $14-3-3{\zeta}$ is overexpressed. In OSCC cells, $14-3-3{\zeta}$ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, $14-3-3{\zeta}$ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-${\gamma}$ (IFN-${\gamma}$) and lipopolysaccharide (LPS). Furthermore, supernatants from $14-3-3{\zeta}$ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with $14-3-3{\zeta}$ and its disruption relieved the inhibition induced by $14-3-3{\zeta}$ in tumor inflammation. Taken together, our studies provide evidence that $14-3-3{\zeta}$ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.