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Assessment of the cytotoxic effects of aporphine prototypes on head and neck cancer cells

  • Dorival Mendes Rodrigues-Junior
  • Nicolie Melanie de Almeida Pontes
  • Gabriela Estrela de Albuquerque
  • Viviane Carlin
  • Givago Prado Perecim
  • Cristiano Raminelli
  • André Luiz VettoreEmail author
PRECLINICAL STUDIES
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Summary

Purpose Among alkaloids, abundant secondary metabolites in plants, aporphines constitute a class of compounds with interesting biological activities, including anticancer effects. The present study evaluated the anticancer activities of 14 substances, including four aporphine derivatives acquired through the biomonitoring of (±)-apomorphine hydrochloride total synthesis from 2-phenethylamine and 3,4-dimethoxybenzaldehyde against head and neck squamous cell carcinoma (HNSCC). Methods The cytotoxic effects of compounds against a panel of HNSCC cell lines were determined by PrestoBlue cell viability assay, while the genotoxicity of substances was evaluated by micronucleus test. Cell death was detected by flow cytometry (Annexin V/7AAD) and western blot analysis was used to detect the presence of cleaved Caspase-3 molecules. Results The aporphine and isoquinoline derivatives APO, C1, and A5 significantly reduced HNSCC cell viability and promoted DNA damages in these cells. Further, by activating the Caspase-3 pathway, these substances were able to induce apoptosis. Conclusion Our results revealed that APO, C1, and A5 exhibit cytotoxic effects in HNSCC cells. The mechanisms of action appear to be partly via the generation of DNA damages and apoptosis induction through Caspase-3 pathway activation. This study provides preclinical data that suggest a potential therapeutic role for APO, C1, and A5 against head and neck cancer cells.

Keywords

Aporphine prototypes Cytotoxic molecules Cancer cells Head and neck cancer 

Notes

Funding

This study was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (2015/09182–0 and 2017/21990–0). D.M.R.-Jr received a scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, 99999.007922/2014–00) and the São Paulo Research Foundation (FAPESP, 2015/21420–3). G.P.P. also received a scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, 1655331). Both N.M.A.P. and A.L.V. had scholarships from the Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (123641/2017–9 and 300936/2015–0, respectively).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

This study was approved by the institutional ethics committee (CEP-UNIFESP: 7428290317).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Dorival Mendes Rodrigues-Junior
    • 1
    • 2
  • Nicolie Melanie de Almeida Pontes
    • 2
  • Gabriela Estrela de Albuquerque
    • 1
    • 2
  • Viviane Carlin
    • 2
  • Givago Prado Perecim
    • 3
  • Cristiano Raminelli
    • 3
  • André Luiz Vettore
    • 1
    • 2
    Email author
  1. 1.Departamento de Ciências BiológicasCampus Diadema, Universidade Federal de São PauloDiademaBrazil
  2. 2.Laboratório de Biologia Molecular do CâncerUniversidade Federal de São PauloSão PauloBrazil
  3. 3.Departamento de Química, Campus DiademaUniversidade Federal de São PauloDiademaBrazil

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