Related Experiment Video
Updated: Oct 9, 2025
Author Spotlight: Recreating Melanoma Complexity with Patient-Derived Organoids for Immunotherapy Evaluation
Published on: September 6, 2024
Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells
Irene Rodríguez1, Ester Saavedra1,2, Henoc Del Rosario1
1Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad de Las Palmas de Gran Canaria, 35016 Las Palmas de Gran Canaria, Spain.
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 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.
Insights
This study shows a specific chalcone derivative effectively induces apoptosis in human melanoma cells. The compound triggers cell death pathways, offering a potential new strategy for melanoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Melanoma incidence is rising globally, necessitating novel therapeutic strategies.
- Targeting apoptosis is a promising approach for melanoma treatment.
- Chalcones are investigated for their potential anticancer properties.
Purpose of the Study:
- To evaluate a novel chalcone derivative as an apoptosis inducer in human melanoma cells.
- To elucidate the molecular mechanisms underlying chalcone-induced melanoma cell death.
Main Methods:
- Treatment of human melanoma cell lines (SK-MEL-1, MEL-HO) with the chalcone derivative.
- Assessment of apoptosis markers including cytochrome c release and PARP cleavage.
- Analysis of reactive oxygen species generation, apoptotic pathway activation, and key protein expression (TRAIL, DR4, DR5, p21, NF-κB).
Main Results:
- The chalcone derivative potently induced apoptosis in melanoma cells.
- Cell death involved mitochondrial cytochrome c release and PARP cleavage, blocked by caspase inhibitors.
- Mechanisms included reactive oxygen species generation, activation of intrinsic/extrinsic apoptotic and MAPK pathways, TRAIL/DR4/DR5 upregulation, p21 downregulation, and NF-κB inhibition.
Conclusions:
- The studied chalcone is a potent inducer of apoptosis in human melanoma.
- Its mechanism involves multiple signaling pathways, highlighting its therapeutic potential.
- This chalcone derivative warrants further investigation for melanoma treatment.
More Related Videos
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
06:09Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway
01:30Apoptosis
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...