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

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.

Silver nanoparticles as proapoptotic drugs: pharmacological basis in non-metastatic skin melanoma

“…54 The discovery of substances that activate apoptotic pathways lead to antiproliferative agents. 55…”

“…Currently, the NPs of iron, silver, gold, zinc and copper are the most studied due to their properties. 55 These are structures with sizes less than 100 nanometers (ie 1x10 -7 meters), which can be synthesized from different materials. 56,57 Authors consider that the green synthesis of AgNPs opened a new era for the diagnosis and treatment of cancer.…”

Synthesis of new hybrid pyridines catalyzed by Fe3O4@SiO2@urea-riched ligand/Ch-Cl

“…Hybrid pyridines as distinguished scaffolds of heterocyclic compounds not only are extensively present in pharmaceutical active molecules, agricultural compounds and functional materials 54 – 58 but also are one of the most top-selling drugs and can serve as treatment of Alzheimer’s diseases 59 , anticancer 60 and antihypertensive 61 . Intriguingly, hybrid molecules bearing pyridine, indole and sulfonate moieties have exceptional potential in pharmaceutical and medicinal chemistry such as antioxidant, antiapoptosis, antidyslipidemia, antitumorigenic, antiinflammatory and can enhance the stability and solubility of drugs 62 – 67 . A number of biologically active hybrid molecules bearing pyridine, indole and sulfonate moieties are sketched in Fig.…”

Chalcone-Acridine Hybrid Suppresses Melanoma Cell Progression via G2/M Cell Cycle Arrest, DNA Damage, Apoptosis, and Modulation of MAP Kinases Activity

“…In the last decade we documented the antiproliferative effect of several chalcone derivatives such as acridine hybrids [ 36 , 37 , 38 ], indole hybrids [ 39 , 40 , 41 ] or cyclic chalcone analogues [ 42 , 43 , 44 ] using different in vitro cancer models such as breast, colorectal or cervix cancers. Furthermore, both the antiproliferative and anticancer effects of chalcones have also been documented using melanoma cancer cells or melanoma xenografts [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ].…”