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.

5-Methoxytryptophan Sensitizing Head and Neck Squamous Carcinoma Cell to Cisplatitn Through Inhibiting Signal Transducer and Activator of Transcription 3 (STAT3)

“…A previous study reported that 5-MTP dose dependently reduces the growth of oral cancer cells, and the IC 50 values of the OC3-I5 and OC3 cells are 400 and 1000 mM, respectively (16). Our results indicated that 5-MTP inhibited the growth squamous cells, whereas the IC 50 values of the SCC4 and SCC25 cells were 2.7 and 3.1 mM, respectively.…”

“…A murine A549 xenograft tumor model demonstrated that the intraperitoneal injection of 5-MTP significantly reduces tumor growth up to 50% when compared with the vehicle control (15). Furthermore, 5-MTP reduces the invasion and metastasis of oral cancer in vitro and vivo (16). However, the antioral cancer mechanism of 5-MTP remains unclear.…”

Elevated Systemic L-Kynurenine/L-Tryptophan Ratio and Increased IL-1 Beta and Chemokine (CX3CL1, MCP-1) Proinflammatory Mediators in Patients with Long-Term Titanium Dental Implants

“…A new role for L-trp metabolites has been proposed in bone metabolism. Apalset et al demonstrated an association between kynurenine pathway metabolites and bone metabolism in patients since bone mineral density was associated with high serum concentrations of two interferon γ-induced kynurenines (xanthurenic acid, and 3-hydroxyanthranilic acid) [33].…”

5-Methoxytryptophan enhances the sensitivity of sorafenib on the inhibition of proliferation and metastasis for lung cancer cells

“…Additionally, the inhibitory effect of 5-MTP on EMT, cancer cell migration, and metastasis is achieved by inhibiting cyclooxygenase (COX)-2 expression [22]. Moreover, 5-MTP has been shown to reduce invasion and metastasis of oral cancer both in vitro and in vivo [23]. In a murine A549 xenograft tumor model, intraperitoneal injection of 5-MTP significantly reduced tumor growth by up to 50% compared to the vehicle control [24].…”