Few studies have evaluated the apoptosis-inducing efficacy of NaF on cancer cells in vitro but there has been no previous investigation of the apoptotic effects of NaF on human oral squamous cell carcinoma cells. In this study, we have investigated the mechanisms underlying the apoptotic response to NaF treatment in the YD9 human squamous cell carcinoma cell line. The viability of YD9 cells and their growth inhibition were assessed by MTT and clonogenic assays, respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to detect apoptosis. YD9 cells were treated with NaF, and western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, and MMP and proteasome activity assays were performed sequentially. The NaF treatment resulted in a time- and dose-dependent decrease in YD9 cell viability, a dose-dependent inhibition of cell growth, and the induction of apoptotic cell death. The apoptotic response of these cells was manifested by nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, a significant shift of the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF treatment resulted in the downregulation of G1 cell cyclerelated proteins, and upregulation of p53 and the Cdk inhibitor p27KIP1. Taken collectively, our present findings demonstrate that NaF strongly inhibits YD9 cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via mitochondrial and caspase pathways.

The use of bacteria in the treatment of cancer has a long and interesting history. The use of live bacteria in this way however has a number of potential problems including toxicity. Purified low molecular weight bacterial proteins have therefore been tested as anticancer agents to avoid such complications. Oral cancer is a widely occurring disease around the world and these lesions are typically very resistant to anticancer agents. In our present study we investigated the effects of purified recombinant azurin from Pseudomonas (P.) aeruginosa against YD-9 (p53-positive) human oral squamous carcinoma cells. Azurin showed cytotoxic effects against these cells in a dose dependent manner. The cell death accompanied by this treatment was found to be characterized by chromatin condensation and apoptotic bodies. Azurin treatment was further found to increase the expression of p53 The stabilization of p53 and induction of apoptosis in YD-9 cells by azurin suggests that it has potentially very strong anticancer properties in oral squamous carcinoma.

Oral squamous cell carcinoma (SCC) is one of the leading causes of cancer mortality worldwide. It is generally thought that adjuvant chemotherapy provides modest prolongation of survival in various carcinoma. Docetaxel (Taxotere, TXT) play a significant role in the treatment of various solid tumors of epithelial origin. CsA (immunosuppressive drug) was widely used as adjunct for the treatment of cancer. Thus, it is important to pursue the apoptosis of IHOK and oral SCC induced by TXT combined with CsA related to the pathogenesis of oral SCC. But TXT combined CsA effect on IHOK and oral SCC remains unclear. After cultured IHOK and HN 22 oral squamous cell carcinoma cell line treated by 10 nM TXT and 1 μM, and caspase inhobitor, respectively, apoptosis index, cytochrome c and caspase-3 -8, -9 mRNA expression by RT-PCR, and procaspase-3 protein amount by immunoslot blotting was prepared. The purpose of this study were to examine the TXT-induced apoptosis pathway via caspase activation by CsA enhancement, and to apply these results to an effective therapeutic treatment plan for oral SCC by TXT combined CsA . 10 nM TXT showed about 60%, 55% celluar apoptosis of IHOK and HN 22, cell line, respectively, while CsA alone did not induce apoptosis in IHOK and HN 22 cell line. 1 μM CsA combined with 10 nM TXT increased apoptosis in IHOK and HN 22 cell line through caspase-3 and cytochrome c mRNA expression, while could not effect on caspase-8 and -9. Caspase inhibitor suppressed apoptosis of IHOK and HN 22 cell line induced by a combination of 1 μM CsA and 10 nM TXT. Immnoslot blotting showed procaspase-3 activation by a combination 1 μM CsA and 10 nM TXT, while caspase inhibitor inhibited activation. It suggested that a combination of CsA and TXT might induce increased apoptosis of IHOK and HN 22 oral squamous cell carcinoma cell line through caspase-3 activation. This treatment with a combination of TXT and CsA may be an effective therapeutic strategy for oral squamous cell carcinoma

The organotypic raft culture model has been shown to be a useful method for examining the effects of biochemical manipulation on various epithelial cell types, using in vitro conditions that simulate the in vivo environment of the tissue of origin. To investigate this method as a model for photodynamic therapy (PDT), we cultures the oral squamous carcinoma cell line YD-10B on fibroblast-containing collagen gels at the air-liquid interface and assessed the efficacy of PDT using a photosensitiser 5-ALA-hexenyl ester. PDT effect on YD-10B organotypic raft cultures after twenty- four hours was determined. The number of residual cells was significantly reduced in comparison to control at all four different conditions. PCNA immunostaining and TUNEL assay revealed that PDT inhibited cell proliferation and increased apoptosis. These findings suggest that the organotypic raft culture model provides an effective and rapid laboratory method of investigating strategies for PDT on oral precancerous lesions and squamous cell carcinomas

Epigallocatechin-3-gallate (EGCG) and theaflavins (TF) are polyphenols included in green and black teas, respectively. Both green and black teas have been studied for their potential health benefits for cancer. Hypoxia-inducible factor (HIF) has been implicated multiple physiological and pathophysiological pathways, particularly, oncogenesis. But, the molecular pathways that govern the cell response to EGCG are not fully elucidated. The present study investigated the intracellular mechanism in oral squamous cell carcinoma (OSCC) cells treated with EGCG, focusing on HIF-1 expression and its effect on epithelial phenotype. EGCG decreased phosphorylated Raf-1 protein in YD 8 OSCC cell, but B-raf protein was not affected at all by EGCG and TF. In addition, we here found that EGCG regulated HIF-1α expression independent of Raf-1 protein. Taken together with our previous result, the result imply that EGCG is attributed to the HIF-1α expression via Raf/MEK/ERK pathway, and the HIF-1α expression is associated with the change of epithelial phenotype in OSCC cell.

Cytosolic Ca2+ is an important regulator of tumor cell proliferation and metastasis. Recently, the strategy of blocking receptors and channels specific to certain cancer cell types has emerged as a potentially viable future treatment. Oral squamous cell carcinoma is an aggressive form of cancer with a high metastasis rate but the receptor-mechanisms involved in Ca2+ signaling in these tumors have not yet been elucidated. In our present study, we report that bradykinin induces Ca2+ signaling and its modulation in the human oral squamous carcinoma cell line, HSC-3. Bradykinin was found to increase the cytosolic Ca2+ levels in a concentration-dependent manner. This increase was inhibited by pretreatment with the phospholipase C-β inhibitor, U73122, and also by 2-aminoethoxydiphenyl borate, an inhibitor of the inositol 1,4,5-trisphosphate receptor. Pretreatment with extracellular ATP also inhibited the peak bradykinin-induced Ca2+ rise. In contrast, the ATP-induced rise in cytosolic Ca2+ was not affected by pretreatment with bradykinin. Pretreatment of the cells with either forskolin or phorbol 12-myristate 13-acetate (activators of adenylyl cyclase and protein kinase C, respectively) prior to bradykinin application accelerated the recovery of cytosolic Ca2+ to baseline levels. These data suggest that bradykinin receptors are functional in Ca2+ signaling in HSC-3 cells and may therefore represent a future target in treatment strategies for human oral squamous cell carcinoma.

Chios gum mastic (CGM) is a resin produced from the stem and leaves of Pistiacia lentiscus L var chia, a plant which grows only on Chios Island in Greece. CGM has been used for many centuries as a dietary supplement and folk medicine for stomach and duodenal ulcers in many Mediterranean countries and is known also to induce cell cycle arrest and apoptosis in some cancer cells. In this study, we further investigated the induction and mechanisms underlying the apoptotic response to CGM treatment in the SCC25 human tongue squamous cell carcinoma cell line. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingival fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay, respectively. Staining with Hoechst and hemacolor dyes and TUNEL assays were employed to detect SCC25 cells undergoing apoptosis. SCC25 cells were treated with CGM, and this was followed by western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, MMP activity and proteasome activity analyses. CGM treatment of SCC25 cells was found to result in a time- and dosedependent decrease in cell viability, a dose-dependent inhibition of cell growth, and apoptotic cell death. Interestingly, CGM showed a remarkable level of cytotoxicity in SCC25 cells but not in normal cells. Tested SCC25 cells also showed several lines of apoptotic manifestation. Taken together, our present findings demonstrate that CGM strongly inhibits cell proliferation by modulating the expression of G1 cell cycle-related proteins and induces apoptosis via the proteasome, mitochondria and caspase cascades in SCC25 cells.

Tumor cells under hypoxic conditions are often found due to the rapid outgrowth of their vascular supply, and,in order to survive hypoxia, these cells induce numerous signaling factors. Erk is an important kinase in cell survival, and its activity is regulated by Raf kinases through numerous growth factor receptors. The authors investigated Erk activation and Raf/Erk signaling using the hypoxia-mimetic agent, cobalt chloride (CoCl2), in oral squamous cell carcinoma (OSCC) cells. CoCl2 increases Erk phosphorylation in both a dose- and time-dependent manner. In addition, blocking the activation of epidermal growth factor receptor (EGFR) using PD168393 abolished Erk activation in response to CoCl2, suggesting that Erk phosphorylation by CoCl2 is dependent on EGFR.

Epithelial-mesenchymal transition (EMT) can play an important role in carcinogenesis of oral squamous cell carcinoma (OSCC). EMT is characterized by morphological and phenotypical change of epithelial cells into mesenchymal cells, and transcriptional repressor of E-cadherin, Snail is critical for EMT. In order to investigate the role of Snail and E-cadherin in OSCC, we analyzed the immunohistochemical pattern of Snail and E-cadherin in 18 OSCCs. The expression of Snail in the OSCC was increased whereas the expression of E-cadherin in the OSCC was decreased in comparison with those of normal oral mucosa, showing reverse correlation. Especially, the fibroblasts near the islands of OSCC showed the positivity of Snail, suggesting the reactive fibroblasts to the EMT of epithelial tumor cells. In metastatic squamous cell carcinoma in cervical lymph node, the positivity of Snail of tumor cells was higher than that of primary OSCC. We concluded that the increased Snail expression and the decreased E-cadherin expression were involved in the progression, invasion and metastasis of OSCC.

Amino acid transporters are essential for the growth and proliferation in all living cells. Among the amino acid transporters, the system L amino acid transporters are the major nutrient transport system responsible for the Na+-independent transport of neutral amino acids including several essential amino acids. The L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed in cancer cells to support their continuous growth and proliferation. 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid(BCH) is a model compound for study of amino acid transporter as a system L selective inhibitor. We have examined the effect and mechanism of BCH on cell growth suppression in FaDu human head and neck squamous cell carcinoma. The BCH inhibited the L-leucine transport in a concentration-dependent manner with a IC 50 value of 43.8±4.3μM. The majority of L-leucine uptake is, therefore, mediated by LAT1 in FaDu cells. The growth of FaDu cells was inhibited by BCH in the time- and concentration- dependent manners. The formation of DNA ladder was not observed with BCH treatment in the cells. Furthermore, the proteolytic processing of caspase-3 and caspase-7 in the cells was not detected by BCH treatment. These results suggest that the BCH inhibits the growth of FaDu human head and neck squamous cell carcinoma through the intracellular depletion of neutral amino acids for cell growth without apoptotic processing

Anti-proliferation of methanol extract of Curcuma rhizome on oral squamous cell carcinoma (KB) and osteosarcoma (HOS) cells were investigated. In order to elucidate the involvement of telomerase inhibitory activity as a part of anti-proliferative effect of Curcuma rhizome on cancer cells, we measured telomerase activity in Curcuma rhizome extract-treated cancer cells. The concentration inhibited cell proliferation to 50% (IC50)of the methanol extract of Curcuma rhizome against oral squamous cell carcinoma (KB) cells and osteosarcoma (HOS) cells were 21.30 μg/mℓ and 39.3μg/mℓ respectively. The methanol extract of Curcuma rhizome showed inhibitory telomerase inhibitory effect which is required for cancer cell immortality. Therefore, it seems that the anticancer effect of methanol extract of Curcuma rhizome is at least partially due to telomerase inhibitory effect. Five fraction samples were prepared according to its polarity differences and analyzed anti-proliferative effects of each fraction samples on oral squamous cell carcinoma and osteosarcoma cells. Anticancer effect was observed in dichloromethane, and ethylacetate fractions. The highest anticancer effect was found in dichloromethane fraction which had IC50value of 23.3 μg/mℓ and 10.5μg/mℓ against oral squamous cell carcinoma (KB) cells and osteosarcoma (HOS) cells, respectively.

Oral squamous cell carcinoma (OSCC) is the most common malignancy and is a major cause of worldwide cancer mortality. The proto-oncogene c-myb plays an important role in regulation of cell growth and differentiation, and it is expressed at high levels in hematopoietic cells and many other types of cancers. However, the function of c-myb is not well known in OSCC. The present study aimed to reveal the function of c-myb and to test the alternation of cell growth and signaling by c-myb in OSCC. In this study, c-myb and dominant-negatibe myb(DNmyb) were expressed in an adenovirus-mediated gene delivery system to KB cells. The over-expressed c-myb brought increased cellular proliferation compared with control cells. However, DN-myb infected KB cells showed significant reduction of cell growth and enhanced induction of apoptosis to activate PARP and caspase 9. c-myb induced increase of IGF-I, -II and IGF-IR expressions while DN-myb down-regulated these expression. Activation of ERK and Akt/PKB pathway was shown only in c-myb transduced cells. These findings suggest that the role of c-myb in cell growth of oral cancer cells is partially mediated through the modulation of IGFs, ERK and Akt/PKB. From this results, DN-myb is strongly recommended as a curable gene for the treatment of c-myb dependent malignancies such as OSCC.

The human ELAV(embryonic lethal abnormal vision)-like protein HuR stabilizes a certain group of cellul ar mHNAs that contain AU- rich elements in their 3’ - untranslated region , To test the significance of HuR in carcinogenesis of head and neck squamous cell carcinomas(HNSCCs), we have investigated HuH expression from 32 benign epithelial lesions , 14 prema lignant epitheli al lesions and 80 HNSCCs, There were two different staining patterns of HuR in HNSCCs : nuclear expression was seen in 78 7% (63 of 80) 01' cases; and an additional cyto plasmic expression was seen in 28, 7%(23 of 80) 01 cases, Nuclear expression of HuR was s ignificantly increased in premalignant lesions and HNSCCs, whereas increased cytoplasπli c expression of HuR was only observed in HNSCCs Cytoplasmic HuR expression was significantly increased in pa tients of HNSCC younger than 60 yea rs , Al though there was no significant correlation between a natomic s ites of HNSCCs and HuR express ion , cyto plasmic HuR expression was highly increased in HNSCCs of larynx, There was no significant co rrela tion between HuR expression and other clinicopathological parameters such as histological type‘ tumor s ize‘ 0 1' n odal s tatus , ln conclusion, this study s uggests that overexpression of HuR in HNSCCs may be part of a regula tory pathway tha t co ntro ls the mHNA stability 0 1' several important targets in carcinogenesis of HNSCCs

A case of a distinctive variety of basalαd squamous cell carcinoma (B8CC) of the floor of mouth is described Histologic evaluation of the tumor showed lobules and aggregates of medium-sized basaloid cells with distinctive periph eral palisading and focal areas of comedo- necrosis. This appearance together with microcystic spaces simulated that of an adenoid cystic carcinoma. Accompanying epithelial dysplasia of the overlying mucosa was found. Immunohistochemistry of the tumor revealed diffuse strong expression for cytokeratin AE1/3, focally positive for Epithelial Membrane Antigen in the inner cells of tubular structures However, CEA, 8-100, smooth muscle actin, and vimentin were negative. The histologic differential diagnosis considered were adenoid cystic carcinoma and adenosquamous cell carcinoma Immunohistochemistry and awareness of this unusual pattern of B8CC will facilitate the correct diagnosis being reached.

The purpose of this study was to evaluate the role 0 1' integrin a 3 and integrin ß 1 in the oral squamous cell ca rcinomas. For this study‘ 10 specimens diagnosed as squamous cell carcinoma referred to the Dept. of Oral Pathology. School of Dentis try, Kyung Hee Univers ity, and 5 specimens of normal oral mucosa without any inflammatory cha nges were used as experimenta l and co nt rol groups, respectively. AlI s pecimens; experirnental and control group were f ixed in neutral f ormalin so lu tion and embedded in paraffin, and then the serial tissue section were rnade 5i1m in thickness and processed for imrnunohi stochemical observatlon The specimens were incubated with prirnary antibody against integrin a 3 r integrin ß 1‘ each was diluted at 1;100, followed by the super sensit ive non- biotin horse r adish peroxidase detection sys tem with DAB as chromogen‘ After counters ta ining with Gill ’s hematoxylin stain method and mounted and examined under the light microscope. Based on the intens ity of the immunoreactivity, intensity of the immunity was scored no ep ithelial stain, weak 0 1' focal epitheli al sta in, modera te 0 1' focal intensive epithelial stain, intense genera lized epitheli al s taining for the e pithelia l, and co nnective ti ssue component in squamous cell carcinomas, and normal oral mucosa on each Expression of integrin a 3 in t he oral mucosa was negli gible. Expression 0 1' integrin a 3 in expression in the or al s mnus cell ca rcinoma was ve ry wea k, but the express ion was increased in poorly differ entiat ed type of the oral squamous cell carcinomas ln the oral mucosa , expression of in tegr in ß 1 ra nged from weak to moderate in the cytoplasm and the cell membra nes of the kera tini zed and basal cell layer. Nuclei were mainly integrin ß 1 negative‘ but rarely revealed weak expression. ln sq uamous cell carcinoma, expression of integrin ß 1 was ntense notably in the cytoplasm, cell membrane a nd nuclear membra ne Nuclei of several tumor cells revealed moderate expression of integrin ß 1. Expression of integrin ß 1 was increased the poorly diffe rentiated type of in squamous cell carcinoma compare to that in moderate or well diffe rentiated type of oral squamous cell carCllìoma These results suggest integrin a 3 and integrin ß 1 may be influ enced the development and growth of the squamous cell carcima .

Oral squamous carcinoma (OSC) is the most common malignant neoplasm of the oral mucosa. Although the etiology of OSC is not fully understood, accumulated evidences indicate that the activation of proto-oncogenes and the inactivation of tumor suppressor genes underlie the disease development. An OSC cell line, YD-9 was newly established and characterized. However, the mutational analysis of p53 gene was not performed. Thus, in this study, the presence of mutation in the p53 gene was examined by amplification of exon-4 to -8 and subsequent DNA sequencing. Two point mutations were found in exon-4 and -6: A to G, resulting in amino acid change Tyr to Cys in exon-4, and C to G, resulting in amino acid change Gly to Arg in exon-6, respectively. Any mutation was not found in the exon-5, -7 and -8. The presented results would contribute to basic research to understand the biological mechanism of OSC using YD-9 cells.

Although a number of molecules have been implicated in the metastasis of oral squamous cell carcinoma (OSCC) , the precise molecular mechanisms that deterrnine the direction of rnigration and invasiveness of OSCC cells into the lymph nodes remain unclear, Chemokines are a superfarnily of small structurally related heparin- binding proteins‘ which have been identified as attractants that control the rnigration of leukocytes‘ especia lly during imrnune and inflammatory reactlOns Moreover, recent studies have demonstrated that several types 。f cancer express chemokine receptor‘s and use chemokines to metastasize to the target organ, However, there h ave been few reports on biological behaviors by downregulation 0 1' CXCR-4 in ora l cancel‘ cells We tried to screen several OSCC cell lines in order to obtain a suitable cell line model which had the cha ract eris tic of the constitutive ly expressed state of CXCR• 4 Of the several OSCC cell lines, only KOSCC-25B showed the high expression of CXCR-4 in both RT-PCR and Western blot analysis, siRNA-CXCR-4 infected subclones of KOSCC-25B(Si, 3‘ Si 1이 showed downregulation of CXCR-4 expression as expected‘ At serum-free co ndi tion‘ Si.3 s ubclone s ignif icantly decreased cell proliferations at 24 h and 48h and Si, lO subclone significant ly dec reased cell proliferations at 24 h Si ,3 clone dec reased to 67 ,4% and Si,lO clone to 65 ,5% in comparison to vector infected cells These data suggest that the downregulation of CXCR-4 expression could induce anti-rnigratory and ant i- rni g ratory effect

Oral squamous cel1 carcinoma(OSCC) is the most common malignancy of head neck region. Typically OSCC cells s how persist ent invasion that frequently leads to local recurrence and distant lymphatic metastasls However, molecular mechanisms of invasion of OSCC remain poorly understood. Her e we identifi ed periostin, interferon induced transmembrane protein l (IF1TM1) and wingless-type MMTV integration site family, member 5B(WNT5B) , as invasion promoting molecules in OSCC by comparing gene expression profiles between a parent OSCC cell line(MSCC-l) and its highly invasive clone(MSCC-1nvl). Overexpression of periostin, IFITMl and WNT5B mRNAs were confirmed in MSCC-1nvl by RT-PCR. Transfection of these molecules promoted invasion of OSCC cells Moreover , siRNA t r eatment of these molecules suppressed invasion of cancer cells in vitro I nter estingly, Periostin, 1F1TMl and WNT5B were highly expressed in OSCCs in comparison with nonnal tissues. 1n an orthotopic mouse model of OSCC, periostin-overexpressing cells metas tasized spontaneously to cervical lymph nodes and t o t he lung through their aggressive invasiveness. These findings suggest that peri ostin, IFITMl and WNT5B play important roles for invasion and of OSCC and can be prognostic markers and therapeutic t argets of OSCC.

Matrix metalloproLeases(MMPs) a re a family of zinc dependent enzymes with the capacity to degrade extracellular matrix prote ins. MMPs express ion correlates with cancer cell invasiveness and metas taslS The purpose of our sωdy was t。 determine the role 0 1' stroma l fïbrob lasts in ca ncer cell invasi on by examining the expression and activity of MMP-2 and -9 We used a YD- lOB squalllous ca rcinoma cell line that was est a blished in Yonsei Univer s ity ‘ College 0 1' Dentistry. We then appli ed two types of s lrolllal fibroblastsdel‘ ived from normal gingival tissue and cancer supporting ti ss ue Morphologic examination of fïbroblas ls was carried out by rnicroscopy and doubling time was measured by MTI assay . YD-lOB cells were cultured by lh ree-d imensional culture using collagen gel with two types of flbroblasts To examine the stromal - mesenchyma l inleraclion. we used a direct co-cul tu re system between YD-IOB cells and fibroblasts. Gelatin zymography was performed to exa llline MMP-2 a ncl 9 activit ies. We found that cancer-derived fibroblasts di splay stel late-shaped cells wi th many cyLopl asmic processes. whereas normal gingi val fibroblasts were spindle shaped. The c1oubling time of bOLh lïbroblasLs was not statistically different. Three-dimensional co-culture 0 1' ca ncer cells with ca n cer- c1erived fïbroblasts induced the formation 0 1' multi - Iayered atypical cells, as compared to culturing with normal gin gival f lbrobl asts Both three-c1 imens ional culture ti ss ues inclucecl the invasive gro￦th of cancer cells into the dermal eq uival enLs . Gelatin zymography s howecl that gelatinolytic activity of MMP-2 was activaterl in both co-culture models. However , MMP-9 ac li vity was not a lterecl in YD-lOB carcinoma cells In conclusion. enhanced MMP-2 activity was inc1 uced by boLh cance r- c1eri vecl a ncl norlllal gingival fibroblasts. suggesting that the potential to invacle by stromal fibroblasts was noL l imilecl to ca ncer- c1 eri ved lïbroblasts

It is well known that the imbalance between epithelial cell growth and inhibitor factors may cause human epithelial cancer. Over-expression of the epidermal growth factor receptor(EGFR) has been implicated in the development of oral squamous cell carcinoma. ZD1839 inhibits selectively the EGFR tyrosine kinase activity and is clinically used for cancer patients. However the mechanisms by which it exerts its anti-tumor activity remains unclear. This study attempted to determine the mechanisms underlying the effects of ZD1839 on the cellular level and to characterize the effects of ZD1839 with regard to human oral squamous cell carcinoma(OSCC) cell growth. The YD-10B and YD-38 cell lines established from OSCC in the department of Oral Pathology, Yonsei University College of Dentistry and ZD1839(Iressa) were used for this study. The inhibition of cell proliferation induced by ZD1839 was reversible and the lowest dose of ZD1839 that produced statistically significant growth inhibition in YD cell lines were 0.1 μM. The delay in cell cycle progression was induced by 0.1 μM of ZD1839 treatment after 24 hr. This reduction in cell proliferation and cell cycle delay were associated with up-regulation of the cyclin dependent kinase inhibitor(CDKI), P21CIP1/WAF1 and P27KIP1. Reduced expression of cyclin D1 was also observed after treatment with ZD 1839 to YD-38 cells but not to YD-38. The present results suggest that the antiproliferative effects of ZD1839, in vitro was associated with degradation of cyclin D1, which may be used as a possible indicator of a high cell sensitivity to ZD1839.