Geoffroea decorticans fruit extracts inhibit the wnt/b-catenin pathway, a therapeutic target in cancer Gabriela C. Somaini a , Manuel J. Aybar a, b , Nancy R. Vera c, ** , Celeste Tríbulo a, b, * a Instituto Superior de Investigaciones Biol ogicas (INSIBIO, CONICET-UNT), San Miguel de Tucum an, Argentina b Instituto de Biología “Dr. Francisco D. Barbieri”, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucum an, San Miguel de Tucum an, Argentina c C atedra de Farmacoquímica, Instituto de Estudios Farmacol ogicos “Dr. Antonio R. Sampietro”, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucum an, San Miguel de Tucum an, Argentina article info Article history: Received 15 December 2020 Accepted 26 January 2021 Keywords: Fruit extracts Geoffroea decorticans Cell signaling Wnt/b-catenin pathway Ethnobotany Xenopus laevis abstract Geoffroea decorticans (cha~ nar) is commonly used for culinary and medicinal purposes in rural commu- nities. The aim of this work was to chemically characterize three Geoffroea decorticans extracts and determine their capacity to modulate the wnt/b-catenin pathway. This signaling pathway plays a key role in embryonic development but its overactivation leads to cancer cell growth. Phytochemical analysis of extracts showed presence of major classes of phytochemicals. Gas chromatography-mass spectrometry results revealed the presence of acids, esters and furanic compounds. Using Xenopus embryos as in vivo model organisms, we found that the extracts modulated dorso-ventral axis formation and rescued hyperdorsalized phenotypes produced by LiCl treatment. In agreement with these findings, Geoffroea decorticans extracts decreased b-catenin levels and suppressed the expression of wnt target genes such as xnr3 and chordin, thus demonstrating an inhibitory regulation of the wnt/b-catenin signaling pathway. All these results support a new role for Geoffroea decorticans fruit derivatives with possible anti- carcinogenic actions. © 2021 Elsevier Inc. All rights reserved. 1. Introduction In the last few years, numerous studies have explored the ability of natural compounds to modulate signaling pathways associated with cancer development [1]. The wnt/b-catenin cell-signaling is an extensively studied pathway involved in various biological pro- cesses. However, aberrantly activated wnt signaling can lead to a wide range of pathologies, including cancer. The inhibition of b- catenin mediated signaling represents a promising strategy for early chemopreventive intervention [2]. A few years ago, it was demonstrated that the blockade of constitutive wnt activity effec- tively inhibits cancer cell growth in vitro [3]. Some natural com- pounds able to modulate wnt/b-catenin signaling have been proposed as anticancer substances [4,5]. Geoffroea decorticans (commonly named cha~ nar) is a vegetal species widely distributed in the center and north of Argentina, north of Chile, south of Peru, and Bolivia. Its fruits (drupes) and its products are commonly used for both culinary and traditional medicinal purposes by rural communities [6]. The most popular product made from cha~ nar fruits is a sweet jelly-like syrup called arrope, used both as a sweetener and as a cough syrup in traditional medicine [7]. Recently, anti-oxidant anti-inflammatory and anti- nociceptive polyphenolic compounds from Geoffroea decorticans have been described. These biological activities have validated the ancestral use of Geoffroea decorticans although no pharmacological effects on signaling pathways have been described until now. Xenopus laevis embryos were extensively used as a model or- ganism to elucidate the functioning and regulation of the wnt/b- catenin signaling pathway. This pathway promotes the activation of dorsal specific genes required to pattern the body axis and its deregulation leads to abnormal stereotypic phenotypes [8]. Abbreviations: GdAE, Geoffroea decorticans aqueous extract; GdChE, Geoffroea decorticans chloroformic extract; GdAcE, Geoffroea decorticans ethyl acetate extract. * Corresponding author. Instituto de Biología “Dr. Francisco D. Barbieri”, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucum an, Chacabuco 461, T4000ILI, San Miguel de Tucum an, Argentina. ** Corresponding author. C atedra de Farmacoquímica, Inst. de Estudios Farm- acol ogicos “Dr. Antonio R. Sampietro”, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucum an, Ayacucho 471, 4000, Tucum an, Argentina. E-mail addresses: nrvera@gmail.com (N.R. Vera), celtribulo@gmail.com (C. Tríbulo). Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc https://doi.org/10.1016/j.bbrc.2021.01.087 0006-291X/© 2021 Elsevier Inc. All rights reserved. Biochemical and Biophysical Research Communications 546 (2021) 118e123