The Endogenous Metabolite 5-Methoxytryptophan as a Potential Novel Therapy for Pancreatic Cancer

Pancreatic adenocarcinoma is a highly aggressive cancer, and due to a lack of early detection methods, is often diagnosed in the late stages of the disease. One reason for the poor prognosis in pancreatic cancer is the repopulation of tumors, which is driven by pathological cyclooxygenase-2 production. The L-tryptophan metabolite 5-MTP has previously been shown to reduce COX-2 transcription via the p300 histone acetyltransferase. In a scratch test assay using the PANC-28 cell line, we demonstrated that PANC-28 cell invasion could be reduced by treatment with 5-MTP at the micromolar level. This project included molecular modeling of 5-MTP at the PGE2 receptor EP3. 5-MTP showed a strong binding score, in a similar location to that of the endogenous prostaglandins. A cell counting kit was used to measure cell survival following 5-MTP administration, and showed that 5-MTP was non-toxic to cells. Given our results, it is possible that 5-MTP may have a beneficial role in pancreatic cancer. Future studies will include biochemical and ligand binding assays to build upon these findings.