Please use this identifier to cite or link to this item:
http://hdl.handle.net/10553/113060
Title: | Apoptosis pathways triggered by a potent antiproliferative hybrid chalcone on human melanoma cells | Authors: | Rodríguez, Irene Saavedra Díaz, Ester Gloria Del Rosario, Henoc Perdomo Díaz, Juan Quintana Aguiar, José Martín Prencipe, Filippo Oliva, Paola Romagnoli, Romeo Estévez, Francisco |
Keywords: | Apoptosis Caspases Cytotoxicity Extracellular Signal-Regulated Kinases Hybrid Chalcones, et al |
Issue Date: | 2021 | Journal: | International Journal of Molecular Sciences | Abstract: | 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 mitochon-drial 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. | URI: | http://hdl.handle.net/10553/113060 | ISSN: | 1661-6596 | DOI: | 10.3390/ijms222413462 | Source: | International Journal of Molecular Sciences [ISSN 1661-6596], v. 22 (24), 13462, (Diciembre 2021) |
Appears in Collections: | Artículos |
Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.