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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

3380 - A new natural compound identified with metabolomic approach has cytotoxic activity against human colorectal cancer cell lines with acquired resistance to cetuximab

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Vincenzo De Falco

Citation

Annals of Oncology (2018) 29 (suppl_8): viii1-viii13. 10.1093/annonc/mdy268

Authors

V. De Falco, E.F. Giunta, V. Belli, N. Matrone, S. Napolitano, E. Martinelli, P. Vitale, N. Zanaletti, M. Terminiello, P.P. Vitiello, F. Ciardiello, T. Troiani

Author affiliations

  • Dipartimento Di Medicina Di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 - Naples/IT
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Resources

Abstract 3380

Background

The discovery of bioactive compounds from natural sources is an important resource to develop new weapons against cancer. In a previous study, we have used a rapid NMR-based metabolomic approach to select plant species belonging to Fabaceae family with anti-proliferative properties. Fourteen species of this family were studied with high-resolution 2D NMR spectroscopy and then several molecules were purified from plant extracts. The family of Fabaceae is widely distributed in the Northern hemisphere and putative pharmacologic effects are described in traditional Chinese pharmacopoeia.

Methods

We analysed the cytotoxic activity of an Astragalus boeticus compound on a panel of human colon cancer cell lines sensitive (SW48, GEO and CACO-2) and with acquired resistance to anti-EGFR inhibitors such as cetuximab (SW48-CR, GEO-CR and CACO-2-CR).

Results

Among a panel of human CRC cell lines, three with acquired resistance to cetuximab (SW48-CR, GEO-CR and Caco-2-CR) were highly sensitive to the Astragalus compound. The treatment with this compound determines a transition to an epithelial phenotype in all three cell lines with reduction of vimentin and an increase of E-cadherin expression. Moreover, Astragalus treatment determines an induction of apoptosis and a significant increase in cell death in SW48-CR, GEO-CR and Caco-2-CR cells, but not in the parental cell lines. These findings were confirmed by western blot assay with activation of caspase cascade only in cetuximab-resistant cells. Moreover, the antiproliferative effect of Astragalus compound on cetuximab-resistant cells is mediated by the inhibition of AKT/mTOR signalling pathway. In particular, western blot analyses have shown a significant reduction in the expression of 4-EBP1 and p-4EBP1 in cetuximab-resistant cell lines following Astragalus treatment. Moreover, the combined treatment with cetuximab and Astragalus induced a synergistic antiproliferative and apoptotic effects with blockade in AKT/mTOR pathway in h cetuximab-resistant cells.

Conclusions

Astragalus compound induces antiproliferative activity in a panel of human CRC with acquired resistance to cetuximab by inhibiting AKT/mTOR pathway.

Clinical trial identification

Legal entity responsible for the study

Università degli Studi della Campania Luigi Vanvitelli.

Funding

Università degli Studi della Campania Luigi Vanvitelli.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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