Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells
| Autor: | Irene Rodríguez, Ester Saavedra, Henoc del Rosario, Juan Perdomo, José Quintana, Filippo Prencipe, Paola Oliva, Romeo Romagnoli, Francisco Estévez |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Indoles
mitogen-activated protein kinase QH301-705.5 hybrid chalcones Article Catalysis NO Inorganic Chemistry Chalcones Cell Line Tumor melanoma Apoptosis Caspases Cytotoxicity Extracellular signal-regulated kinases Hybrid chalcones Melanoma Mitogen-activated protein kinase Reactive oxygen species Humans Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy reactive oxygen species Cell Death Organic Chemistry apoptosis Cytochromes c General Medicine caspases cytotoxicity extracellular signal-regulated kinases Mitochondria Computer Science Applications Chemistry Proto-Oncogene Proteins c-bcl-2 Poly(ADP-ribose) Polymerases Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences; Volume 22; Issue 24; Pages: 13462 International Journal of Molecular Sciences, Vol 22, Iss 13462, p 13462 (2021) International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms222413462 |
| Popis: | The World Health Organization reported that approximately 324,000 new cases of melanoma skin cancer were diagnosed worldwide in 2020. The incidence of melanoma has been increasing over the past decades. Targeting apoptotic pathways is a potential therapeutic strategy in the transition to preclinical models and clinical trials. Some naturally occurring products and synthetic derivatives are apoptosis inducers and may represent a realistic option in the fight against the disease. Thus, chalcones have received considerable attention due to their potential cytotoxicity against cancer cells. We have previously reported a chalcone containing an indole and a pyridine heterocyclic rings and an α-bromoacryloylamido radical which displays potent antiproliferative activity against several tumor cell lines. In this study, we report that this chalcone is a potent apoptotic inducer for human melanoma cell lines SK-MEL-1 and MEL-HO. Cell death was associated with mitochondrial cytochrome c release and poly(ADP-ribose) polymerase cleavage and was prevented by a non-specific caspase inhibitor. Using SK-MEL-1 as a model, we found that the mechanism of cell death involves (i) the generation of reactive oxygen species, (ii) activation of the extrinsic and intrinsic apoptotic and mitogen-activated protein kinase pathways, (iii) upregulation of TRAIL, DR4 and DR5, (iv) downregulation of p21Cip1/WAF1 and, inhibition of the NF-κB pathway. |
| Databáze: | OpenAIRE |
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