Carbidopa alters tryptophan metabolism in breast cancer and melanoma cells leading to the formation of indole-3-acetonitrile, a pro-proliferative metabolite

• Autor(a) principal: Duarte, D
• Data de Publicação: 2019
• Outros Autores: Amaro, F, Silva, I, Silva, D, Fresco, P, Oliveira, JC, Reguengo, H, Gonçalves, J, Vale, N
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/10216/136253
• topic: A375 cell line; Carbidopa; Indole-3-acetonitrile; MCF-7 cell line; Tryptophan

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 andmelanoma. Recently, itwas 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.