Assessment of the cytotoxic effects of aporphine prototypes on head and neck cancer cells
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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.
KeywordsAporphine prototypes Cytotoxic molecules Cancer cells Head and neck cancer
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.
This study was approved by the institutional ethics committee (CEP-UNIFESP: 7428290317).
- 2.Hostettmann K, Potterat O, Wolfender JL (1998) The potential of higher plants as a source of new drugs. Chimia 52:10–17Google Scholar
- 9.Kashiwada Y, Aoshima A, Ikeshiro Y, Chen YP, Furukawa H, Itoigawa M, Fujioka T, Mihashi K, Cosentino LM, Morris-Natschke SL, Lee KH (2005) Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids. Bioorg Med Chem 13:443–448CrossRefGoogle Scholar
- 26.Schwab RS, Amador LV, Lettvin JY (1951) Apomorphine in Parkinson's disease. Trans Am Neurol Assoc 56:251–253Google Scholar
- 39.Deigner HP, Kinscherf R (1999) Modulating apoptosis: current applications and prospects for future drug development. Curr Med Chem 6:399–414Google Scholar
- 41.Montririttigri K, Moongkarndi P, Joongsomboonkusol S, Chitkul B, Pattanapanyasat K (2008) Apoptotic activity of aporphine from Stephania venosa on human ovarian cancer cells. Mahidol University J Pharm Sci 35:52–56Google Scholar