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Biochem Biophys Res Commun
2021 Mar 26;546:118-123. doi: 10.1016/j.bbrc.2021.01.087.
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Geoffroea decorticans fruit extracts inhibit the wnt/β-catenin pathway, a therapeutic target in cancer.
Somaini GC
,
Aybar MJ
,
Vera NR
,
Tríbulo C
.
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Geoffroea decorticans (chañar) is commonly used for culinary and medicinal purposes in rural communities. The aim of this work was to chemically characterize three Geoffroea decorticans extracts and determine their capacity to modulate the wnt/β-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 β-catenin levels and suppressed the expression of wnt target genes such as xnr3 and chordin, thus demonstrating an inhibitory regulation of the wnt/β-catenin signaling pathway. All these results support a new role for Geoffroea decorticans fruit derivatives with possible anti-carcinogenic actions.
Fig. 1. Geoffroea decorticans extracts generate ventralized phenotypes in Xenopus embryos. Cephalic region is at the right. (A) Control embryo. (B) GdAE 10 mg/ml (C) GdAE 20 mg/ml (D) GdAE 30 mg/ml. (E) Quantification of abnormal phenotypes. (F) GdChE 0.5 mg/ml (G) GdChE 1 mg/ml (H) GdAcE 0.5 mg/ml (I) GdAcE 1 mg/ml. (J) Quantification of abnormal phenotypes.
Fig. 2. Geoffroea decorticans extracts rescue LiCl dorsalized embryos. (A) Normal control sibling untreated embryo. Cephalic region is at the right. (B) LiCl treated embryo. Rescue experiments were performed by incubating the LiCl treated embryos with (C) GdAE (30 mg/ml), (D) GdChE (0.5 mg/ml) or (E) GdAcE (0.5 mg/ml). (F) DAI analysis results after LiCl (DAI = 7.2) and GdAE (DAI = 5.4), GdChE (DAI = 5.6), GdAcE (DAI = 5.1) treatment. (G–J) chd gene expression by in situ hybridization labeling. Vegetal pole view. (G) Control embryo. (H) GdAE (30 mg/ml). (I) LiCl induced an ectopically augmented expression of chd. (J) LiCl plus GdAE. Expanded chd expression was reversed. Cg: cement gland. D: dorsal. OpV: optic vesicle. V: ventral.
Fig. 3. Geoffroea decorticans extracts exert an inhibitory effect on wnt/β-catenin genes. (A) Xenopus embryos were treated with LiCl and then cultured with GdChE (1 mg/ml) and GdAcE (0.5 mg/ml). After LiCl treatment, xnr3 and chd expression decreased in animal caps while β-catenin expression increased. After treatment with G. decorticans extracts, the expression of all these genes decreased. Results are expressed as Relative Intensity (Sample/GADPHx10). Student’s t-test was used. Differences were considered statistically significant at P < 0.0001(∗). (B) Control embryo, normal β-catenin Y654 levels. Embryos treated with (C) GdAE (30 mg/ml), (D) GdChE (1 mg/ml) and (E) GdAcE (0.5 mg/ml). Note the decrease in phospho-β-catenin Y654 levels compared to the control. (F) Quantification of (B-E). ap, animal pole. bl, blastocoel. vp, vegetal pole.
