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

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.

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Acknowledgments

We acknowledge the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, MCTI, Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, MEC, Brazil), Fundação de Apoio à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC, State of Santa Catarina, Brazil), Consejo Nacional de Investigaciones Cientifícas y Tecnicas (CONICET, Argentina), Agencia Nacional de Promocion Cientifíca y Tecnologica (ANPCyT, Argentina) and UBA (Universidad de Buenos Aires, Argentina) for the financial support (grant numbers 472979/2011-6 and 2671/2012-9 from CNPq and PRONEX/FAPESC, respectively) as well as for our research fellowships.

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Correspondence to Cláudia Maria Oliveira Simões.

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Silva, I.T., Geller, F.C., Persich, L. et al. Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549. Invest New Drugs 34, 139–148 (2016). https://doi.org/10.1007/s10637-015-0317-4

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Keywords

  • Cucurbitacins
  • Apoptosis
  • Invasion
  • Metastasis