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Planta Med 2018; 84(18): 1372-1379
DOI: 10.1055/a-0651-8141
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Triterpenoids from Momordica balsamina with a Collateral Sensitivity Effect for Tackling Multidrug Resistance in Cancer Cells

Cátia Ramalhete
1   Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
2   ATLÂNTICA – Escola Universitária de Ciências Empresariais, Saúde, Tecnologias e Engenharia, Oeiras, Portugal
,
Silva Mulhovo
3   Centro de Estudos Moçambicanos e de Etnociências, Faculty of Natural Sciences and Mathematics, Pedagogical University, Maputo, Mozambique
,
Hermann Lage†
4   Institute of Pathology, University Hospital Charité, Berlin, Germany
5   Department of Pathology, Vivantes Clinics, Berlin, Germany
,
Maria-José U. Ferreira
1   Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
› Author Affiliations
Further Information

Publication History

received 27 March 2018
revised 05 June 2018

accepted 22 June 2018

Publication Date:
11 July 2018 (online)

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Abstract

The collateral sensitivity effect is among the most promising strategies for overcoming multidrug resistance in cancer. In this work, 28 cucurbitane-type triterpenoids (1–28), previously isolated from the African medicinal plant Momordica balsamina and its derivatives, were evaluated for their collateral sensitivity effect on three different human cancer entities, gastric (EPG85-257), pancreatic (EPP85-181), and colon (HT-29), each with two different multidrug-resistant variants. One was selected for its resistance to daunorubicin (EPG85-257RDB, EPP85-181RDB, HT-29RDB) and the other was selected for its resistance to mitoxantrone (EPG85-257RNOV, EPP85-181RNOV, HT-29RNOV). On gastric cell lines, the best results were obtained for compounds 3 and 10, which exhibited a collateral sensitivity effect together with high antiproliferative activity. In turn, on colon cancer cell lines, the best multidrug resistance-selective antiproliferative effects were observed for derivatives 11, 13, and 15, which showed collateral sensitivity effects against both resistant variants. Compounds 11 and 3 were also the most selective against the multidrug resistance pancreatic cells lines. Some compounds, such 6, 10, 11 and 15, were previously found to be strong P-glycoprotein modulators, thus highlighting their potential as promising leads for overcoming multidrug resistance in cancer cells.

Key words

Momordica balsamina - Cucurbitaceae - collateral sensitivity - antiproliferative activity - multidrug resistance - triterpenes

Supporting Information

    Physicochemical properties of compounds 1 – 28 are available as Supporting Information.

  • Supporting Information
 

  • References

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