S-Allylcysteine inhibits tumour progression and the epithelial-mesenchymal transition in a mouse xenograft model of oral cancer.
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.
Department of Anatomy, Taipei Medical University, Taiwan, ROC.
Man-Hui
MH
Pai
Yueh-Hsiung
YH
Kuo
En-Pei Isabel
EP
Chiang
Feng-Yao
FY
Tang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D019938:Cyclin D1; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D019085:Fluorescent Antibody Technique, Direct; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy*; D016328:NF-kappa B; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000517:prevention & control; D053495:Osteopontin / Q000097:blood / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D009363:Neoplasm Proteins; D053495:Osteopontin; D019938:Cyclin D1; C065299:S-allylcysteine; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D003545:Cysteine