Evaluation of Uliginosin B as a Modulator of the Ras Pathway: In Vivo Evidence From Caenorhabditis elegans and In Silico Insights
Maria Eduarda O. De Souza, Flávia Suelen De O. Pereira, Daniela Teixeira Rodrigues, Helder Dias Costa, Tarsila Dantas Da Rosa, Camila Machado Pires da Silva, Gilsane von Poser, Stela M. K. Rates, Favero R. Paula, Daiana Silva ÁvilaABSTRACT
Previously, in vitro studies have suggested a possible antiproliferative action of uliginosin B (ULI B), a dimeric acylphloroglucinol isolated from Hypericum species. However, no in vivo evidence of this effect has been found yet. Therefore, the aim is to evaluate its possible interaction in the Ras pathway using the nematode Caenorhabditis elegans and computational models. For the in vivo assays, we used a strain with a gain‐of‐function in the let‐60 gene, which is a human Ras homologous protein that leads to the formation of tumorous multivulva. The experimental tests indicated that a single 30 min treatment with ULI B was safe regarding toxicological parameters, and the worms demonstrated a delay in the multivulva phenotype development (MV) on day 1 and 2 of adulthood, with statistical significance at 5, 10, and 20 µM. In silico, ULI B showed a possible allosteric and non‐competitive interaction with LET‐60, but not as significant as in the human Ras, possibly justifying the weak effect found with the delay in MV development in the nematode. However, based on the in‐silico data, ULI B seems promising against human cancer cells, as its interactions with EGFR and HRAS were more favorable than those with C. elegans proteins.