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Metabolomic approach for a rapid identification of natural products with cytotoxic activity against human colorectal cancer cells.

Metabolomic approach for a rapid identification of natural products with cytotoxic activity against human colorectal cancer cells.
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Graziani V, Scognamiglio M, Belli V, Esposito A, D'Abrosca B, Chambery A, Russo R, Panella M, Russo A, Ciardiello F, Troiani T, Potenza N, Fiorentino A,


Graziani V, Scognamiglio M, Belli V, Esposito A, D'Abrosca B, Chambery A, Russo R, Panella M, Russo A, Ciardiello F, Troiani T, Potenza N, Fiorentino A, (click to view)

Graziani V, Scognamiglio M, Belli V, Esposito A, D'Abrosca B, Chambery A, Russo R, Panella M, Russo A, Ciardiello F, Troiani T, Potenza N, Fiorentino A,

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Scientific reports 2018 03 288(1) 5309 doi 10.1038/s41598-018-23704-9

Abstract

The discovery of bioactive compounds from natural sources entails an extremely lengthy process due to the timescale and complexity of traditional methodologies. In our study, we used a rapid NMR based metabolomic approach as tool to identify secondary metabolites with anti-proliferative activity against a panel of human colorectal cancer cell lines with different mutation profiles. For this purpose, fourteen Fabaceae species of Mediterranean vegetation were investigated using a double screening method:H NMR profiling enabled the identification of the main compounds present in the mixtures, whilst parallel biological assays allowed the selection of two plant extracts based on their strong anti-proliferative properties. Using high-resolution 2D NMR spectroscopy, putative active constituents were identified in the mixture and isolated by performing a bio-guided fractionation of the selected plant extracts. As a result, we found two active principles: a cycloartane glycoside and protodioscin derivative. Interestingly, these metabolites displayed a preferential anti-proliferative effect on colon cancer cell lines with an intrinsic resistance to anti-EGFR therapies. Our work provides an NMR-based metabolomic approach as a powerful and efficient tool to discover natural products with anticancer activities circumventing time-consuming procedures.

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