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

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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.

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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).

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Authors and Affiliations

  1. Departamento de Ciências Biológicas, Campus Diadema, Universidade Federal de São Paulo, Diadema, Brazil

    Dorival Mendes Rodrigues-Junior, Gabriela Estrela de Albuquerque & André Luiz Vettore

  2. Laboratório de Biologia Molecular do Câncer, Universidade Federal de São Paulo, São Paulo, Brazil

    Dorival Mendes Rodrigues-Junior, Nicolie Melanie de Almeida Pontes, Gabriela Estrela de Albuquerque, Viviane Carlin & André Luiz Vettore

  3. Departamento de Química, Campus Diadema, Universidade Federal de São Paulo, Diadema, Brazil

    Givago Prado Perecim & Cristiano Raminelli

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  1. Dorival Mendes Rodrigues-Junior
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  2. Nicolie Melanie de Almeida Pontes
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Correspondence to André Luiz Vettore.

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

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Rodrigues-Junior, D.M., de Almeida Pontes, N.M., de Albuquerque, G.E. et al. Assessment of the cytotoxic effects of aporphine prototypes on head and neck cancer cells. Invest New Drugs 38, 70–78 (2020). https://doi.org/10.1007/s10637-019-00784-6

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