Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Invest New Drugs
2020 Feb 01;381:70-78. doi: 10.1007/s10637-019-00784-6.
Show Gene links
Show Anatomy links
Assessment of the cytotoxic effects of aporphine prototypes on head and neck cancer cells.
Rodrigues-Junior DM
,
de Almeida Pontes NM
,
de Albuquerque GE
,
Carlin V
,
Perecim GP
,
Raminelli C
,
Vettore AL
.
???displayArticle.abstract???
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.
2015/09182-0 Fundação de Amparo à Pesquisa do Estado de São Paulo (BR), 2017/21990-0 Fundação de Amparo à Pesquisa do Estado de São Paulo (BR), 2015/21420-3 Fundação de Amparo à Pesquisa do Estado de São Paulo (BR)
Antonini,
Apomorphine infusion in advanced Parkinson disease.
2018, Pubmed
Antonini,
Apomorphine infusion in advanced Parkinson disease.
2018,
Pubmed
Chen,
New dimeric aporphine alkaloids and cytotoxic constituents of Hernandia nymphaeifolia.
1996,
Pubmed
Chen,
New aporphine alkaloids and cytotoxic constituents of Hernandia nymphaeifolia.
1997,
Pubmed
Chen,
Apoptosis of a human non-small cell lung cancer (NSCLC) cell line, PLA-801, induced by acutiaporberine, a novel bisalkaloid derived from Thalictrum acutifolium (Hand.-Mazz.) Boivin.
2002,
Pubmed
Chin,
Novel markers for poor prognosis in head and neck cancer.
2005,
Pubmed
Cragg,
Impact of natural products on developing new anti-cancer agents.
2009,
Pubmed
Deigner,
Modulating apoptosis: current applications and prospects for future drug development.
1999,
Pubmed
Gören,
Cytotoxic and DNA damaging activity of some aporphine alkaloids from Stephania dinklagei.
2003,
Pubmed
Hwang,
Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells.
2001,
Pubmed
Iyer,
Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis.
2015,
Pubmed
Jemal,
Global cancer statistics.
2011,
Pubmed
Kashiwada,
Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids.
2005,
Pubmed
Kim,
Tetrathiomolybdate induces doxorubicin sensitivity in resistant tumor cell lines.
2011,
Pubmed
Kondo,
Suppression of tumor cell growth and mitogen response by aporphine alkaloids, dicentrine, glaucine, corydine, and apomorphine.
1990,
Pubmed
Lin,
Thalifaberidine, a cytotoxic aporphine-benzylisoquinoline alkaloid from Thalictrum faberi.
1994,
Pubmed
Liu,
Structural and mechanistic bases of the anticancer activity of natural aporphinoid alkaloids.
2013,
Pubmed
Morales-Ramírez,
The OECD's micronucleus test guideline for single exposure to an agent and the genotox-kinetic alternative.
2017,
Pubmed
Picada,
Genotoxic, neurotoxic and neuroprotective activities of apomorphine and its oxidized derivative 8-oxo-apomorphine.
2005,
Pubmed
Ponnala,
Cytotoxicity of aporphines in human colon cancer cell lines HCT-116 and Caco-2: an SAR study.
2011,
Pubmed
Protais,
Effects of various isoquinoline alkaloids on in vitro 3H-dopamine uptake by rat striatal synaptosomes.
1995,
Pubmed
SCHWAB,
Apomorphine in Parkinson's disease.
1951,
Pubmed
Sarto,
The micronucleus assay in exfoliated cells of the human buccal mucosa.
1987,
Pubmed
Simmonds,
Novel drugs from botanical sources.
2003,
Pubmed
Singh,
Recent advances in anti-HIV natural products.
2010,
Pubmed
Slee,
Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis.
2001,
Pubmed
Stévigny,
Cytotoxic and antitumor potentialities of aporphinoid alkaloids.
2005,
Pubmed
Sun,
Isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/m cell cycle arrest and apoptosis.
2012,
Pubmed
Woo,
Topoisomerase II inhibition by aporphine alkaloids.
1999,
Pubmed
Yan,
Studies on the alkaloids of the bark of Magnolia officinalis: isolation and on-line analysis by HPLC-ESI-MS(n).
2013,
Pubmed
