s-allylcysteine and Mouth-Neoplasms

Oral cancer is prevalent worldwide. Studies have indicated that an increase in the osteopontin (OPN) plasma level is correlated with the progression of oral cancer. Our previous report showed that the aqueous garlic extract S-allylcysteine (SAC) inhibited the epithelial-mesenchymal transition (EMT) of human oral cancer CAL-27 cells in vitro. Therefore, the present study investigated whether SAC consumption would help prevent tumour growth and progression, including the EMT, in a mouse xenograft model of oral cancer. The results demonstrated that SAC dose-dependently inhibited the growth of oral cancer in tumour-bearing mice. The histopathological and immunohistochemical staining results indicated that SAC was able to effectively suppress the tumour growth and progression of oral cancer in vivo. The chemopreventive effect of SAC was associated with the suppression of carcinogenesis factors such as N-methylpurine DNA glycosylase and OPN. SAC significantly suppressed the phosphorylation of Akt, mammalian target of rapamycin, inhibitor of κBα and extracellular signal-regulated kinase 1/2 in tumour tissues. The results demonstrated that the SAC-mediated suppression of cyclin D1 protein was associated with an augmented expression of the cell-cycle inhibitor p16(Ink4). Furthermore, SAC inhibited the expression of cyclo-oxygenase-2, vimentin and NF-κB p65 (RelA). These results show that SAC has potential as an agent against tumour growth and the progression of oral cancer in a mouse xenograft model.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cyclin D1; Cysteine; Epithelial Cells; Fluorescent Antibody Technique, Direct; Gene Expression Regulation, Neoplastic; Humans; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Experimental; NF-kappa B; Osteopontin; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Staining and Labeling

Oral cancer is a prevalent type of cancer in Asian countries. Several studies indicated that garlic extracts such as diallyl disulfide (DADS) and diallyl trisulfide (DATS) have anticancer effects. However, the inhibitory effects of water soluble garlic extracts, S-allylcysteine (SAC), on the malignant progression of oral cancer have not been studied well yet. Thus, the purpose of this study was to investigate the inhibitory effects of SAC on the proliferation and progression of human oral squamous cancer CAL-27 cells. In the present study, we demonstrated that SAC dose dependently inhibited the growth of human oral squamous cancer cells. Our results showed that SAC induced the expression of E-cadherin adhesion molecule. Immunocytochemical staining result also revealed that SAC could restore the distribution of E-cadherin molecule on cell membrane. We further demonstrated that SAC stabilized the adherent junction complex of E-cadherin/beta-catenin in oral cancer cells. Treatment with the MAPK/MEK specific inhibitor, PD098059, could up-regulate the expression of E-cadherin molecule. Furthermore, SAC significantly inhibited the activation of MAPK/ERK signaling pathway. These findings were associated with the down-regulation of the SLUG repressor protein. In conclusion, our results indicated that SAC effectively inhibited the proliferation, up-regulated the expression of E-cadherin molecule and stabilized the E-cadherin/beta-catenin adherent junction complex in human oral squamous cancer cells. The mechanism of action was in part through the suppression of MAPK/ERK signaling pathway and down-regulation of the SLUG repressor protein.

Topics: Adherens Junctions; Cadherins; Cell Proliferation; Cysteine; Disease Progression; Enzyme Activation; Flavonoids; Humans; MAP Kinase Kinase 2; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases; Mouth Neoplasms; Snail Family Transcription Factors; Transcription Factors; Tumor Cells, Cultured

The effects of S-allylcysteine (SAC) on hepatic lipid peroxidation and antioxidant status during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBP) were investigated in male Syrian hamsters. Enhanced lipid peroxidation in the liver of tumour-bearing animals was accompanied by significant decreases in the activities of glutathione peroxidase (GPx) and glutathione S-transferase (GST) and a reduction in reduced glutathione (GSH) levels. Administration of SAC significantly decreased the formation of lipid peroxides and enhanced the levels of antioxidants and detoxifying enzymes. We suggest that the elevation of hepatic GSH and GSH-dependent enzymes by SAC may play a key role in preventing cancer development in the hamster cheek pouch.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antioxidants; Carcinoma, Squamous Cell; Cheek; Cricetinae; Cysteine; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Lipid Peroxidation; Liver; Liver Neoplasms, Experimental; Male; Mesocricetus; Mouth Neoplasms; Protective Agents; Thiobarbituric Acid Reactive Substances

The effect of S-allylcysteine (SAC), a water-soluble garlic constituent, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis was investigated in male Syrian hamstes. Forty hamsters were divided into 4 groups of 10 animals. The right buccal pouches of the animals in Group I were painted with a 0.5% solution of DMBA in liquid paraffin three times a week. The animals in Group II were painted with DMBA as in Group I and, in addition, received 200 mg/kg body wt p.o. SAC three times a week on days alternate to DMBA application. Group III animals received SAC as in Group II. Group IV animals received neither DMBA nor SAC and served as the control. The hamsters were killed after an experimental period of 14 wk. Measurement of lipid peroxidation, the antioxidant enzymes superoxide dismutase (SOD) and catalase, in the buccal pouch mucosa, liver, and circulation was used to monitor the chemopreventive potential of SAC. All hamsters painted with DMBA alone developed tumors identified histologically as well-differentiated squamous cell carcinomas. In hamsters bearing DMBA-induced buccal pouch tumors, diminished lipid peroxidation in the tumor tissue was accompanied by decreased activities of SOD and catalase, whereas in the liver and circulation, enhanced lipid peroxidation was associated with compromised antioxidant defenses. Administration of SAC suppressed the incidence of DMBA-induced HBP tumors as revealed by the absence of carcinomas. Histologically, only keratosis was observed. SAC modulated DMBA-induced decreased susceptibility of the HBP to lipid peroxidation while simultaneously enhancing SOD and catalase activities, whereas in the liver and circulation, SAC decreased the extent of lipid peroxidation and significantly enhanced antioxidant activities. We suggest that SAC exerts its chemopreventive effects by modulating lipid peroxidation and enhancing antioxidant activities in the target organ as well as in the liver and circulation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Catalase; Cheek; Cricetinae; Cysteine; Epithelium; Erythrocytes; Garlic; Lipid Peroxidation; Liver; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Consumption of garlic has been reported to be associated with decreased risk of cancer. We used the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinoma model to assess the oral chemopreventive potential of S-allylcysteine (SAC), a water-soluble constituent of garlic. Hamsters were divided into four groups of six animals each. The right buccal pouches of the animals in group I were painted with a 0.5% solution of DMBA in liquid paraffin three times a week. The animals in group II were painted with DMBA as in group I and in addition received 200 mg/kg body weight SAC intragastrically three times a week on days alternate to DMBA application. Group III animals received SAC as in group II. Animals in group IV received neither DMBA nor SAC and served as control. The hamsters were killed after an experimental period of 14 weeks. Biochemical measurements were carried out on tumour and normal pouch tissues. Measurement of lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione S-transferase (GST) was used to monitor the chemopreventive potential of SAC. All hamsters painted with DMBA alone for 14 weeks developed well-differentiated squamous cell carcinomas. Diminished lipid peroxidation in the oral tumour tissue was accompanied by a significant increase in the levels of GSH, GPx and GST. Administration of SAC significantly suppressed DMBA-induced oral carcinogenesis as revealed by the absence of neoplasms. The results of the present study suggest that garlic may exert its chemopreventive effects by modulating lipid peroxidation and enhancing the levels of GSH, GPx and GST.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Analysis of Variance; Animals; Antineoplastic Agents; Carcinogens; Carcinoma, Squamous Cell; Cricetinae; Cysteine; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Lipid Peroxidation; Male; Mouth Neoplasms