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Dextran-Catechin Conjugate: A Potential Treatment Against the Pancreatic Ductal Adenocarcinoma

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ABSTRACT

Purpose

A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC).

Methods

The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR and GPC analyses, while the functionalization degree was determined by the Folin-Ciocalteu assay. The biological activity of the catechin-dextran conjugate was tested on two different cell lines derived from human pancreatic cancer (MIA PaCa-2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing cells evaluated.

Results

Both the cancer cell lines are killed when exposed to the conjugate, and undergo apoptosis after the incubation with catechin-dextran which resulted more effective in killing pancreatic tumor cells compared to the catechin alone. Moreover, our experimental data indicate that the conjugate was less cytotoxic to human pancreatic nestin-expressing cells which are considered a good model of non-neoplastic pancreatic cells.

Conclusion

The suitability of newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved confirming the high potential application of the proposed macromolecula system in the cancer therapy.

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ACKNOWLEDGMENTS & DISCLOSURES

This work was financially supported by MIUR (Programma di ricerca di rilevante interesse nazionale 2008), and University of Calabria funds.

Financial support of Regional Operative Program (ROP) Calabria ESF 2007/2013 – IV Axis Human Capital – Operative Objective M2 - Action D.5 is gratefully acknowledged. Authors are solely responsible for the work.

Authors thank Prof. Alfred Cuschieri from the Medical Science lab Scuola Superiore S. Anna, Pisa, Italy.

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Authors and Affiliations

  1. NEST Scuola Normale Superiore & Istituto Nanoscienze-CNR Piazza San Silvestro, 56126, Pisa, Italy

    Orazio Vittorio & Emanuela Jacchetti

  2. Department of Pharmaceutical Sciences, University of Calabria, 87036, Arcavacata di Rende (CS), Italy

    Giuseppe Cirillo, Francesca Iemma, Ortensia Ilaria Parisi, Francesco Puoci & Nevio Picci

  3. Macrofarm Srl, University of Calabria, 87036, Arcavacata di Rende (CS), Italy

    Giuseppe Cirillo, Francesca Iemma, Ortensia Ilaria Parisi, Francesco Puoci & Nevio Picci

  4. Department of Oncology Transplantation & Advanced Technologies in Medicine, University of Pisa, 56100, Pisa, Italy

    Giovanni Di Turi & Niccola Funel

  5. Immunohematology Unit, Cisanello Hospital, 56100, Pisa, Italy

    Michele Curcio & Serena Barbuti

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  1. Orazio Vittorio
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Correspondence to Giuseppe Cirillo.

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Vittorio, O., Cirillo, G., Iemma, F. et al. Dextran-Catechin Conjugate: A Potential Treatment Against the Pancreatic Ductal Adenocarcinoma. Pharm Res 29, 2601–2614 (2012). https://doi.org/10.1007/s11095-012-0790-9

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  • DOI: https://doi.org/10.1007/s11095-012-0790-9

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