Investigational New Drugs

, Volume 34, Issue 2, pp 139–148

Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549

  • Izabella Thaís Silva
  • Fabiana Cristina Geller
  • Lara Persich
  • Sabine Eva Dudek
  • Karen Luise Lang
  • Miguel Soriano Balparda Caro
  • Fernando Javier Durán
  • Eloir Paulo Schenkel
  • Stephan Ludwig
  • Cláudia Maria Oliveira Simões
PRECLINICAL STUDIES

DOI: 10.1007/s10637-015-0317-4

Cite this article as:
Silva, I.T., Geller, F.C., Persich, L. et al. Invest New Drugs (2016) 34: 139. doi:10.1007/s10637-015-0317-4

Summary

Cucurbitacins and their derivatives are triterpenoids that are found in various plant families, and are known for their pharmacological and biological activities, including anti-cancer effects. Lung cancer represents a major public health problem, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer. The objective of this work was to evaluate four cucurbitacins (CUCs) for their cytotoxic activity, effects on apoptosis induction, cell cycle progression, anti-migratory, and anti-invasive effects on the human NSCLC cell line (A549 cells). Our findings showed that these CUCs could suppress human NSCLC cell growth in vitro through their effects on the PI3Kinase and MAPK pathways, which lead to programmed cell death induction, as well as inhibition of cell migration and cell invasion. Additionally, these effects culminate in apoptosis induction and G2/M cell cycle arrest by modulating cyclin B1 expression, and in the mitigation of strategic steps of lung cancer metastasis, including migration and invasion of A549 cells. These results suggest that two natural (DDCB and CB) and two novel semisynthetic derivatives of cucurbitacin B (ACB and DBCB) could be considered as promising compounds with antitumor potential.

Keywords

Cucurbitacins Apoptosis Invasion Metastasis 

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Izabella Thaís Silva
    • 1
  • Fabiana Cristina Geller
    • 1
  • Lara Persich
    • 1
  • Sabine Eva Dudek
    • 4
  • Karen Luise Lang
    • 2
  • Miguel Soriano Balparda Caro
    • 2
  • Fernando Javier Durán
    • 3
  • Eloir Paulo Schenkel
    • 1
  • Stephan Ludwig
    • 4
  • Cláudia Maria Oliveira Simões
    • 1
  1. 1.Departamento de Ciências Farmacêuticas, CIF, CCSUniversidade Federal de Santa Catarina (UFSC)FlorianópolisBrazil
  2. 2.Department of ChemistryUniversidade Federal de Santa CatarinaFlorianópolisBrazil
  3. 3.UMYMFOR – Department of Organic ChemistryUniversidad de Buenos AiresBuenos AiresArgentina
  4. 4.Institute of Molecular Virology, Center of Molecular Biology of InflammationWestfaelische-Wilhelms-UniversityMuensterGermany

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