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Planta Med 2014; 80(18): 1739-1745
DOI: 10.1055/s-0034-1383244
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Diterpenes from Euphorbia piscatoria: Synergistic Interaction of Lathyranes with Doxorubicin on Resistant Cancer Cells

Mariana A. Reis
1   Instituto de Investigação do Medicamento (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
,
Angela Paterna
1   Instituto de Investigação do Medicamento (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
,
Andreia Mónico
1   Instituto de Investigação do Medicamento (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
,
Joseph Molnar
2   Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
,
Hermann Lage
3   Institute of Pathology, Charité Campus Mitte, Berlin, Germany
,
Maria-José U. Ferreira
1   Instituto de Investigação do Medicamento (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
› Author Affiliations
Further Information

Publication History

received 11 June 2014
revised 27 July 2014

accepted 05 October 2014

Publication Date:
05 November 2014 (online)

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Abstract

Four new diterpenes were isolated from the methanolic extract of Euphorbia piscatoria, two ent-abietanes (1, 2) and two lathyrane-type macrocyclic diterpenes (3, 4), along with three known diterpenes (5–7). Their structures were characterized by spectroscopic methods, mainly 1D and 2D NMR (1H, 13C, DEPT, COSY, HMBC, HMQC, and NOESY) experiments. Compound 2, with an unusual structure, might be considered intermediate in the biosynthesis of ent-abietane α,β-unsaturated lactones, commonly found in Euphorbia species. Therefore, a possible biogenetic pathway is proposed. The MDR reversal potential of macrocyclic diterpenes 3–5 was evaluated through a drug combination assay, using the L5178Y mouse T lymphoma cell line transfected with the human MDR1 gene. Compounds 3–5 were able to enhance, synergistically, the antiproliferative activity of doxorubicin (combination indexes < 0.5). Moreover, compounds 1–6 were also assessed for their antiproliferative activity on human MDR cancer cell models, namely gastric, pancreatic, and colon. Weak antiproliferative activity was observed for compounds 1 (IC50 = 66.02 ± 7.10 µM) and 4 (IC50 = 39.51 ± 3.82 µM) on the MDR gastric cell line.

Key words

Euphorbia piscatoria - Euphorbiaceae - lathyrane macrocyclic diterpenes - abietane lactones - MDR-reversal

Supporting Information

 

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