title: 5-Methoxytryptophan-dependent inhibition of oral squamous cell carcinoma metastasis.
abstract: The metastatic status of oral cancer is highly associated with the overall survival rate of patients. Previous studies have revealed that the endogenous tryptophan metabolite 5-methoxytryptophan (5-MTP) can downregulate cyclooxygenase-2 expression; suppress tumor proliferation, migration, and invasion; and reduce the tumor size. To improve the understanding of the molecular mechanisms involved in the regulation of 5-MTP in the tumorigenesis of oral cancer, we conducted a comparative wound healing and transwell invasion assays. Our results revealed that 5-MTP reduce oral cancer cell migration and invasion ability. In addition, the results of an in vivo assay demonstrated that the growth of primary tumors was significantly inhibited by 5-MTP in OC3 oral cancer cells and in invasive OC3-I5 oral cancer cells. Moreover, enlarged spleens were observed in OC3-I5-implanted severe combined immunodeficiency mice although 5-MTP can inhibit spleen enlargement. Through comparative proteomics, we identified 32 differentially regulated protein spots by using 2D-DIGE/MALDI-TOF MS analyses. Some of the differentially regulated proteins such as amadillo-repeat-containing X-linked protein 1, phosphoglycerate kinase 1, tropomyosin alpha-1, and tropomyosin alpha-4 may be associated with the 5-MTP-dependent inhibition of oral cancer growth and metastasis. We conclude that 5-MTP plays a crucial role in inhibiting in vitro and in vivo cancer invasion and metastasis.
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors.forename: Ssu-Han
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan.
authors.forename: Chien-Wen
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Chou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D020543:Proteome / Q000032:analysis / Q000187:drug effects*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D000970:Antineoplastic Agents; D020543:Proteome; C027986:5-methoxytryptophan; D014364:Tryptophan
keywords: 5-Methoxytryptophan; DIGE; Invasion; MALDI-TOF MS; Oral cancer; Proteomics