On Oral Squamous Cell Carcinoma Cell Research Articles

Matrix stiffness mechanically conditions EMT and migratory behavior of oral squamous cell carcinoma.

Tumors are composed of heterogeneous phenotypes, each having different sensitivities to the microenvironment. One microenvironment characteristic - matrix stiffness - helps to regulate malignant transformation and invasion in mammary tumors, but its influence on oral squamous cell carcinoma (OSCC) is unclear. We observed that, on stiff matrices, a highly invasive OSCC cell line (SCC25) comprising a low E-cad to N-cad ratio (InvH/E:NL; SCC25) had increased migration velocity and decreased adhesion strength compared to a less invasive OSCC cell line (Cal27) with high E-cad to N-cad ratio (InvL/E:NH; Cal27). However, InvL/E:NH cells acquire a mesenchymal signature and begin to migrate faster when exposed to prolonged time on a stiff niche, suggesting that cells can be mechanically conditioned. Owing to increased focal adhesion assembly, InvL/E:NH cells migrated faster, which could be reduced when increasing integrin affinity with high divalent cation concentrations. Mirroring these data in human patients, we observed that collagen organization, an indicator of matrix stiffness, was increased with advanced disease and correlated with early recurrence. Consistent with epithelial tumors, our data suggest that OSCC cells are mechanically sensitive and that their contribution to tumor progression is mediated in part by this sensitivity.This article has an associated First Person interview with the first author of the paper.

Oridonin induces G2/M cell cycle arrest and apoptosis in human oral squamous cell carcinoma

Oridonin, an active diterpeniod isolated from Rabdosia rubescens, has been reported for its anti-tumor activity on several cancers, however, its effect on oral squamous cell carcinoma (OSCC) remains unclear. In this study, we demonstrated for the first time that oridonin inhibited the growth of OSCC cells both in vitro and in vivo. Oridonin decreased the proliferation and clonal formation of cultured OSCC cells in a dose-dependent manner. Further study indicated that oridonin induced G2/M phase arrest in OSCC cells, which was associated with the downregulation of proteins related to G2/M transition including cdc25C, cdc2 and cyclin B1, as well as the upregulation of p53 and phosphorylated-cdc2. In addition, we discovered that oridonin induced OSCC cell apoptosis by activating the intrinsic apoptotic pathway, which was indicated by the increased expression of cleaved-caspase 3, cleaved-caspase 9 and proapoptotic protein Bax and reduced expression of caspase 9 and antiapoptotic protein Bcl-xl. Finally, oridonin suppressed the growth of OSCC in an xenograft mouse model. Immunohistochemical analysis showed a reduction of cyclin B1-positive cancer cells and an increase of TUNEL-positive cancer cells in oridonin-treated mice. Therefore, oridonin may be a potentially effective agent for the treatment of OSCC in future.

MiR-375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion.

We aimed to detect the functions of miR‐375/SLC7A11 axis on oral squamous cell carcinoma (OSCC) cell proliferation and invasion. Expression levels of miR‐375 and SLC7A11 in OSCC tissues and cells were measured with RT‐qPCR and western blot. Targeting site was predicted by TargetScan and confirmed by dual luciferase reporting assay. By way of manipulating the expression level of miR‐375 and SLC7A11 in CAL‐27 and Tca8113 cell lines, the cell biological abilities were evaluated. MTT, colony formation, Transwell, wound healing assays and flow cytometry were used to detect OSCC cell viability, proliferation, invasion, migration and apoptosis, respectively. MiR‐375 was significantly downregulated in OSCC tissues and cells compared to adjacent tissue and normal oral cell line respectively while SLC7A11 was upregulated. Targeting relationship was verified by luciferase reporting assay, and miR‐375 could effectively suppress SLC7A11 level in OSCC cells. Replenishing of miR‐375 significantly repressed OSCC cell viability, proliferation, invasion and migration and induced cell apoptosis and G1/G0 arrest. Overexpression of SLC7A11 recovered those biological abilities in miR‐375 upregulated cells. Collective data suggested that miR‐375 served as a tumor suppressor via regulating SLC7A11. Replenishing of miR‐375 or knockout of SLC7A11 could be therapeutically exploited.

Invitro and invivo antitumor effects of chloroquine on oral squamous cell carcinoma.

Chloroquine, which is a widely used antimalarial drug, has been reported to exert anticancer activity in some tumor types; however, its potential effects on oral squamous cell carcinoma (OSCC) remain unclear. The present study aimed to explore the effects and possible underlying mechanisms of chloroquine against OSCC. MTT and clonogenic assays were conducted to evaluate the effects of chloroquine on the human OSCC cell lines SCC25 and CAL27. Cell cycle progression and apoptosis were detected using flow cytometry. Autophagy was monitored using microtubule-associated protein 1A/1B-light chain 3 as an autophagosomal marker. In order to determine the in vivo antitumor effects of chloroquine on OSCC, a CAL27 xenograft model was used. The results demonstrated that chloroquine markedly inhibited the proliferation and the colony-forming ability of both OSCC cell lines in a dose- and time-dependent manner in vitro. Chloroquine also disrupted the cell cycle, resulting in the cell cycle arrest of CAL27 and SCC25 cells at G0/G1 phase, via downregulation of cyclin D1. In addition, chloroquine inhibited autophagy, and induced autophagosome and autolysosome accumulation in the cytoplasm, thus interfering with degradation; however, OSCC apoptosis was barely affected by chloroquine. The results of the in vivo study demonstrated that chloroquine effectively inhibited OSCC tumor growth in the CAL27 xenograft model. In conclusion, the present study reported the in vitro and in vivo antitumor effects of chloroquine on OSCC, and the results indicated that chloroquine may be considered a potent therapeutic agent against human OSCC.

High level of calpain1 promotes cancer cell invasion and migration in oral squamous cell carcinoma.

Calpain1, termed conventional calpain and a member of the Ca2+-dependent neutral cysteine proteases, is considered to be involved in cancer formation and development. However, the effect of calpain1 on oral squamous cell carcinoma (OSCC) remains poorly understood. The aim of the present study was to evaluate the possibility of calpain1 as a potential molecular target for OSCC diagnosis and therapy. The present study demonstrates that calpain1 was overexpressed in OSCC cell lines and 4/7 of the tumor tissues in paired samples of tumor and noncancerous matched tissues (NCMT). In a cohort of 125 patients with primary OSCC, the high expression of calpain1 was an independent predictor for overall survival in a multivariate analysis (P=0.022). Furthermore, RNA interference-mediated suppression of calpain1 expression reduced the proliferation, migration and invasion potential of the HSC3 and CAL27 OSCC cell lines, but did not increase their apoptosis. These findings indicate that calpain1 may be a useful biomarker for novel prognostic and therapeutic strategies in oral squamous cell carcinoma.

Icaritin Reduces Oral Squamous Cell Carcinoma Progression via the Inhibition of STAT3 Signaling.

Icaritin, a traditional Chinese medicine, possesses antitumor activity. The current study aimed to investigate icaritin effect and potential mechanism on oral squamous cell carcinoma (OSCC) development. OSCC cells proliferation, apoptosis, and autophagy were analyzed after incubation with icaritin at different concentrations and incubation times. The expressions of proteins related to proliferation, apoptosis, and autophagy, as well as signal transducer and activator of transcription 3 (STAT3) signal network, were also evaluated by western blot. Furthermore, STAT3 was knocked down by siRNA transfection to determine STAT3 role in OSCC cell proliferation and apoptosis. An oral specific carcinogenesis mouse model was used to explore icaritin effect on OSCC in vivo. Icaritin significantly inhibited OSCC proliferation in vitro and reduced the expression of both the cell-cycle progression proteins cyclin A2 and cyclin D1. Besides, icaritin increased cleaved caspase 3 and cleaved poly-(ADP-ribose) polymerase expression leading to apoptosis, and it activated autophagy. Icaritin significantly inhibited the expression of phospho-STAT3 (p-STAT3) in a dose- and time-dependent manner. In the in vivo experiment, the number of malignant tumors in the icaritin-treated group was significantly lower than the control. Overall, icaritin suppressed proliferation, promoted apoptosis and autophagy, and inhibited STAT3 signaling in OSCC in vitro and in vivo. In conclusion, icaritin might be a potential therapeutic agent against OSCC development.

Wheatgrass: Green Blood can Help to Fight Cancer.

Oral squamous cell carcinoma is the sixth most common cancer worldwide and is one of the leading causes of death especially in developing countries like India. It is usually managed with the help of chemotherapeutic agents that are toxic not only to the tumor cells but also to normal cells in many ways. Whereas the traditional herbal medicines which are used from ancient days in India are generally known to be free of toxic effects and are effective. Wheatgrass is the young grass of the wheat plant 'Tritcumaestivum Linn', family Poaceae (Gramineae). It contains a number of vitamins, mineral, amino acids and vital enzymes, these play an important role in the anticancer approach of this herbal product. It is also called as 'green blood' because of its high content of chlorophyll, which bears a structural similarity to haemoglobin and this result in high oxygen supply to all the body tissues. To analyse the effect of the aqueous wheat grass extract on Oral Squamous Cell Carcinoma (OSCC) cell line by MTT assay. 'KB cell line' (Mouth Epidermal Carcinoma Cells) was used for the present study. Aqueous extract of wheat grass was prepared in the institution. The aim of the study was to assess the effect of the aqueous wheat grass extract on KB cell line(OSCC) by MTT assay. A 41.4% of OSCC cell inhibition was observed at 1000 µg/ml dilution of aqueous wheatgrass extract in 24 hours. The aqueous extract of wheatgrass has an inhibitory effect on the oral cancer cell line proliferation.

Kochia scoparia induces apoptosis of oral cancer cells in vitro and in heterotopic tumors

Ethnopharmacological relevanceKochia scoparia grows commonly in China, Japan, and Korea and its mature fruit has been used throughout the area in traditional medicine to treat diseases including skin problems and inflammatory and allergic disease. More importantly, Kochia scoparia has been prescribed to treat the malignant tumor of head and neck region and breast mass. Although it has been proposed as an anti-cancer agent for several cancers, its exact in vivo anti-cancer properties and the molecular mechanisms underlying its effects are poorly understood. Aim of the studyTo evaluate the anti-cancer activity of the methanol extract of K. scoparia, mature fruit (MEKS) on oral squamous cell carcinoma (OSCC) and to explore its mode of action. Materials and methodsTo assess proliferation inhibition and apoptosis induction by MEKS, MTT assays, cell analysis, ANNEXIN V and PI double staining, and Hoechst 33342 staining were performed. The activation of caspases and the MAP kinase p38 was evaluated using Western blot analysis. The anti-cancer properties of MEKS in vivo were elucidated in a heterotopic OSCC animal model. ResultsAfter OSCC cells were treated with MEKS, the numbers of sub-G1 accumulated cells and apoptotic bodies increased, indicating that MEKS inhibited OSCC cell proliferation selectively through induction of apoptosis. Apoptosis of MEKS-treated OSCC cells was induced in a dose-dependent manner by caspase-3 and -9 activation. In addition, pretreatment with p38 inhibitor SB203580 in combination with MEKS significantly prevented MEKS-induced apoptosis in OSCC cells and also decreased cleaved capase 3, 9, and cleaved PARP activity in western blotting. MEKS treatment significantly increased the apoptosis of OSCC and inhibited tumour growth in our animal model. ConclusionTaken together, these results indicated that MEKS induced apoptosis of OSCC cells through caspase activation involving the p38 MAPK pathway. MEKS could be a promising anti-cancer candidate for OSCC treatment.

The influence of p53 mutation status on the anti-cancer effect of cisplatin in oral squamous cell carcinoma cell lines

ObjectivesThe purpose of this study was to evaluate the anti-cancer activity of cisplatin by studying its effects on cell viability and identifying the mechanisms underlying the induction of cell cycle arrest and apoptosis on oral squamous cell carcinoma (OSCC) cell lines with varying p53 mutation status.Materials and MethodsThree OSCC cell lines, YD-8 (p53 point mutation), YD-9 (p53 wild type), and YD-38 (p53 deletion) were used. To determine the cytotoxic effect of cisplatin, MTS assay was performed. The cell cycle alteration and apoptosis were analyzed using flow cytometry. Western blot analysis was used to detect the expression of cell cycle alteration- or apoptosis-related proteins as well as p53.ResultsCisplatin showed a time- and dose-dependent anti-proliferative effect in all cell lines. Cisplatin induced G2/M cell accumulation in the three cell lines after treatment with 0.5 and 1.0 µg/mL of cisplatin for 48 hours. The proportion of annexin V-FITC-stained cells increased following treatment with cisplatin. The apoptotic proportion was lower in the YD-38 cell line than in the YD-9 or YD-8 cell lines. Also, immunoblotting analysis indicated that p53 and p21 were detected only in YD-8 and YD-9 cell lines after cisplatin treatment.ConclusionIn this study, cisplatin showed anti-cancer effects via G2/M phase arrest and apoptosis, with some difference among OSCC cell lines. The mutation status of p53 might have influenced the difference observed among cell lines. Further studies on p53 mutation status are needed to understand the biological behavior and characteristics of OSCCs and to establish appropriate treatment.

Garcinol inhibits tumour cell proliferation, angiogenesis, cell cycle progression and induces apoptosis via NF-κB inhibition in oral cancer.

Garcinol, a polyisoprenylated benzophenone is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Its ability to inhibit tumour growth has been demonstrated in certain cancers. In this study, we evaluated the potential anti-tumour effects of garcinol on oral squamous cell carcinoma (OSCC) cells. Three OSCC cell lines (SCC-4, SCC-9 and SCC-25) were treated with garcinol for 48h and its effect on growth and proliferation, clonogenic survival, cell cycle and apoptosis was studied by MTT, clonogenic assay, propidium iodide (PI) staining and annexin-V binding assay, respectively. The alteration in expression of NF-κBand COX-2 was studied by western blot analysis and that of VEGF by ELISA. Garcinol treatment significantly (p < 0.001) inhibited the growth and proliferation and colony formation of OSCC cells with a concomitant induction of apoptosis and cell cycle arrest. It did not show toxic effect on normal cells. It significantly (p < 0.05) reduced the expression of NK-κB and COX-2 expression in treated cells as compared to untreated controls besides inhibiting VEGF expression. It appears that garcinol exerts anti-proliferative, pro-apoptotic, cell-cycle regulatory and anti-angiogenic effects on oral cancer cells through inhibition of NF-κB and COX-2. Thus, garcinol may be developed as a potential chemopreventive and/or chemotherapeutic agent for treatment of oral squamous cell carcinoma.

Manumycin A from a new Streptomyces strain induces endoplasmic reticulum stress-mediated cell death through specificity protein 1 signaling in human oral squamous cell carcinoma.

Manumycin A (Manu A) is a natural antibiotic produced by new Streptomyces strain, exhibiting antitumor and anticancer effects. However, the anticancer effects of Manu A on oral squamous cell carcinoma (OSCC) have not been reported. OSCC is an aggressive type of cancer because of its poor prognosis and low survival rate despite advanced medical treatment. We observed that Manu A reduced cell growth and Sp1 protein levels in OSCC cell lines (HN22 and HSC4) in a dose- and time-dependent manner. We also observed downregulation of Sp1 downstream target genes such as p27, p21, Mcl-1 and survivin. Moreover, nuclear staining with DAPI showed that Manu A was able to cause nuclear condensation and further fragmentation. Flow cytometry analyses using Annexin V and propiodium iodide supported Manu A-mediated apoptotic cell death of OSCC cells. Furthermore, Bcl-2 family such as mitochondrial pro‑apoptotic Bax, anti-apoptotic Bcl-xl and Bid were regulated by Manu A, triggering the mitochondrial apoptotic pathway. In conclusion, these results indicate that Manu A is a potential to treat human OSCC via cell apoptosis through the downregulation of Sp1.

Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma.

Licochalcone A (LCA), a chalconoid derived from root of Glycyrrhiza inflata, has been known to possess a wide range of biological functions such as antitumor, anti-angiogenesis, antiparasitic, anti-oxidant, antibacterial and anti-inflammatory effects. However, the anticancer effects of LCA on oral squamous cell carcinoma (OSCC) have not been reported. Our data showed that LCA inhibited OSCC cell (HN22 and HSC4) growth in a concentration- and time-dependent manner. Mechanistically, it was mediated via downregulation of specificity protein 1 (Sp1) expression and subsequent regulation of Sp1 downstream proteins such as p27, p21, cyclin D1, Mcl-1 and survivin. Here, we found that LCA caused apoptotic cell death in HSC4 and HN22 cells, as characterized by sub-G1 population, nuclear condensation, Annexin V staining, and multi-caspase activity and apoptotic regulatory proteins such as Bax, Bid, Bcl(-xl), caspase-3 and PARP. Consequently, this study strongly suggests that LCA induces apoptotic cell death of OSCC cells via downregulation of Sp1 expression, prompting its potential use for the treatment of human OSCC.

Abstract 4976: Telomerase-specific replication-selective virotherapy combined with radiation therapy for oral squamous cell carcinoma cells

Abstract Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We previously, investigated the antitumor effect of the hTERT-specific replication-competent adenovirus (Telomelysin: OBP-301) on oral squamous cell carcinoma (OSCC) cells in vitro and in vivo orthotopic graft model. OBP-301 replicated efficiently and induced more over 50% cell killing in a panel of human OSCC cell lines, but not in normal human fibroblasts, which were lacking telomerase activity. In orthotopic graft model, intratumoral injection of OBP-301 resulted in a significant inhibition of tumor growth and prolongation of survival. Moreover, OBP-301 in use has limited potency when administered alone; however, combination therapy using these agents and conventional anticancer agents, such as radiation exhibits encouraging levels of efficacy. Here, we describe the mechanistic basis for synergy of irradiation and OBP-301. This combination therapy was more effective compared with OBP-301 alone in OSCC cells. These results illustrate the potential of combining oncolytic virotherapy and ionizing radiation as a promising strategy in the management of human oral cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4976. doi:1538-7445.AM2012-4976

Honokiol: a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells

Honokiol (HNK) is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma (OSCC) cells is unknown. We investigated the antitumor activities of HNK on OSCC cells in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and propidium iodide (PI) assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling (TUNEL), and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 μg·mL−1 or 20 μg·mL−1 of HNK were more stronger compared with those of 20 μg·mL−1 5-fluorouracil (5-Fu, the control) applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.

Antitumor activity of suberoylanilide hydroxamic acid against human oral squamous cell carcinoma cell lines in vitro and in vivo

It has been reported recently that histone deacetylase inhibitors (HDACIs) can block the growth of a variety of malignant tumor cells by reversing the silencing of the tumor suppressor genes; these will be the anticancer agents of the next generation. In this study, we evaluated the antitumor effects of the HDACI suberoylanilide hydroxamic acid (SAHA) on oral squamous cell carcinoma (OSCC) and investigated its molecular mechanism. SAHA suppressed the in vitro proliferation of OSCC cell lines in a dose- and time-dependent manner. Flow cytometric analyses showed that treatment with SAHA led to G1 phase cell-cycle arrest of OSCC cells, accompanying a decrease in the percentage of S-phase cells. Western blot analyses demonstrated that the expression of p21 protein was remarkably augmented and hyperacetylation of p53 was induced after SAHA treatment. These results suggest that administration of SAHA suppresses OSCC growth through G1 phase arrest. Additionally, we observed that the growth of xenograft SAS tumors in nude mice was significantly blocked by the administration of SAHA without major adverse effects.

Apoptotic effect of CKD-602 (Camtobell ®) on oral squamous cell carcinoma cell lines

The purposes of this study were to measure the cytotoxic effect of CKD-602 on oral squamous cell carcinoma (OSCC) cell lines, to evaluate the apoptotic aspect of dead cells, and to identify the signaling molecules involved in apoptosis. The human OSCC cell lines A253, HSC-3 and KB were treated with CKD-602. The apoptotic proportion of the cells was analyzed using flow cytometry. The expression of Bax, Bcl-2, and p53 were detected by western blotting analysis. CKD-602 showed excellent cytotoxicity to the OSCC cell lines. Most cell death was attributed to apoptosis rather than necrosis. CKD-602 induced the down-regulation of Bcl-2 in A253 and HSC-3 cells, and p53 was expressed in the KB cell line after treatment with CKD-602.

Cell-surface density of complement restriction factors (CD46, CD55, and CD59): oral squamous cell carcinoma versus other solid tumors

Complement restriction factors (CD46, membrane cofactor; CD55, decay accelerating factor; and CD59, protectin) are overexpressed on tumor cells, and they enable tumor cells to escape from complement-dependent and antibody-mediated killing. Cell-surface density of complement restriction factors (CRFs) on oral squamous cell carcinoma (OSCC) is compared with that found on other solid tumors (breast, pancreas, colon carcinomas, and melanoma) to understand the significance of their diversity. The cell-surface expression of CRFs on tumor cells was confirmed with confocal laser scan fluorescent microscopy. Cell suspension enzyme-linked immunosorbent assay (cs-ELISA), which measures the density of cell-surface antigens, was utilized to study CRFs on the cell surface of tumor cells (OSCC, 2 cell lines; breast, 5 cell lines; pancreas, 3 cell lines; colon, 3 cell lines; and melanoma, 9 cell lines). Confocal laser scan fluorescent microscopy confirmed the expression of CD46, CD55, and CD59 on the cell surface of OSCC cell lines SCC12 and SCC71. The relative densities of cell-surface expression obtained from cs-ELISAs of CRFs on OSCCs are as follows: CD59 > CD55 > CD46. The relative densities of the 3 CRFs in breast and pancreatic carcinomas were similar to those found in OSCCs, whereas the profile of CRFs in melanoma (CD59 > CD55 < CD46) and colon cancer (CD46 > CD55 > CD59) were different. These findings indicate diverse strategies adopted by tumor types to resist antibody-mediated complement-dependent cytotoxicity; possibly the factors (exogenous and endogenous) in their respective microenvironments may play a role in the diversity.

The role of tamoxifen in combination with cisplatin on oral squamous cell carcinoma cell lines

The purpose of this study was to evaluate the effect of tamoxifen (TAM) when used in combination with cisplatin on oral squamous cell carcinoma (OSCC). For this, the relation between estrogen receptor (ER) expression level and the cytotoxic effect of TAM, the apoptotic effect and its molecular mechanisms of TAM were investigated using OSCC cell lines. Combination treatment demonstrated a superior cytotoxic and apoptotic effect on OSCC cell lines. Considerable amount of ER was detected in some OSCC cell lines, but there were no significant differences of cytotoxic effect of TAM. TAM inhibited PKC activity and up-regulated TGF-β1 secretion.

556 Histone deacetylase inhibitors induce chromatin decondensation by down-regulation of proteins involved in the maintenance of heterochromatin

It has been reported recently that histone deacetylase inhibitors (HDACIs) can block the growth of a variety of malignant tumor cells by reversing the silencing of the tumor suppressor genes; these will be the anticancer agents of the next generation. In this study, we evaluated the antitumor effects of the HDACI suberoylanilide hydroxamic acid (SAHA) on oral squamous cell carcinoma (OSCC) and investigated its molecular mechanism. SAHA suppressed the in vitro proliferation of OSCC cell lines in a dose- and time-dependent manner. Flow cytometric analyses showed that treatment with SAHA led to G1 phase cell-cycle arrest of OSCC cells, accompanying a decrease in the percentage of S-phase cells. Western blot analyses demonstrated that the expression of p21 protein was remarkably augmented and hyperacetylation of p53 was induced after SAHA treatment. These results suggest that administration of SAHA suppresses OSCC growth through G1 phase arrest. Additionally, we observed that the growth of xenograft SAS tumors in nude mice was significantly blocked by the administration of SAHA without major adverse effects.