NDLI: Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells

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Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells

Content Provider	MDPI
Author	Irene, Rodríguez Francisco, Estévez Saavedra, Ester Rosario, Henoc del Perdomo, Juan Quintana, José Prencipe, Filippo Oliva, Paola Romagnoli, Romeo
Copyright Year	2021
Description	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 $p21^{Cip1/WAF1}$ and, inhibition of the NF-κB pathway.
Starting Page	13462
e-ISSN	14220067
DOI	10.3390/ijms222413462
Journal	International Journal of Molecular Sciences
Issue Number	24
Volume Number	22
Language	English
Publisher	MDPI
Publisher Date	2021-12-15
Access Restriction	Open
Subject Keyword	International Journal of Molecular Sciences Dermatology Apoptosis Caspases Cytotoxicity Hybrid Chalcones Extracellular Signal-regulated Kinases Melanoma Mitogen-activated Protein Kinase Reactive Oxygen Species
Content Type	Text
Resource Type	Article

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