Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite
Diana Duarte,
Filipa Amaro,
Isabel Silva,
Dany Silva,
Paula Fresco,
José C. Oliveira,
Henrique Reguengo,
Jorge Gonçalves,
Nuno Vale
Affiliations
Diana Duarte
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Filipa Amaro
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Isabel Silva
Clinical Chemistry, Department of Laboratory Pathology, Centro Hospitalar Universitário do Porto (CHUP), Largo Prof. Abel Salazar, 4099-313 Porto, Portugal
Dany Silva
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Paula Fresco
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
José C. Oliveira
Clinical Chemistry, Department of Laboratory Pathology, Centro Hospitalar Universitário do Porto (CHUP), Largo Prof. Abel Salazar, 4099-313 Porto, Portugal
Henrique Reguengo
Clinical Chemistry, Department of Laboratory Pathology, Centro Hospitalar Universitário do Porto (CHUP), Largo Prof. Abel Salazar, 4099-313 Porto, Portugal
Jorge Gonçalves
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Nuno Vale
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Carbidopa is used for the treatment of Parkinson’s disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa.
