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: Ssu-Han Wang, Chien-Wen Chang, Hsiu-Chuan Chou
• Journal: Electrophoresis (Electrophoresis) Vol. 36 Issue 17 Pg. 2027-34 (Sep 2015) ISSN: 1522-2683 [Electronic] Germany
• PMID: 26171676 (Publication Type: Journal Article)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• Proteome
• 5-methoxytryptophan
• Tryptophan

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Female
• Humans
• Mice
• Mice, Nude
• Mouth Neoplasms (metabolism, pathology)
• Neoplasm Invasiveness
• Proteome (analysis, drug effects)
• Proteomics
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Tryptophan (analogs & derivatives, pharmacology)
• Two-Dimensional Difference Gel Electrophoresis