Melanoma is one of the most chemoresistant cancers in patient care. The remission rate of current therapy remains low. DC-81, an antitumor antibiotic produced by Streptomyces species, belongs to pyrrolo[2,1-c][1,4]benzodiazepine (PBD), which is a potent inhibitor of nucleic acid synthesis. An enediyne contains either DNA intercalating groups or DNA minor groove binding functions and these are potent DNA-damaging agents due to their ability to generate benzenoid diradicals. We have previously reported an efficient synthesis and antitumor activity of a series of novel PBD hybrids linked with enediyne. The purpose of this study was to examine the mechanism of the antiproliferative effect of DC-81-enediyne agent on human melanoma A375 cells. DC-81-enediyne induced an increase in Ca(2+) level and reactive oxygen species (ROS) generation as detected by flow cytometric assay. Western blot analysis showed that DC-81-enediyne induced the phosphorylation of p38 and activating transcription factor 2 (ATF-2). By using the luciferase reporter assay, activating protein-1 (AP-1) activity was further enhanced after A375 cells were treated with graded concentrations of DC-81-enediyne. DC-81-enediyne treatment-induced A375 cell apoptosis was significantly abrogated by the addition of Ca(2+), ROS, and p38 inhibitors. Collectively, our studies indicate that DC-81-enediyne induces A375 cell apoptosis through an increased Ca(2+) and ROS generation, which involves p38 phosphorylation and enhanced ATF-2/AP-1 expressions, leading to caspase-3 activity, poly(ADP-ribose)polymerase cleavage, M30 CytoDeath staining, and subsequent apoptotic cell death.
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http://dx.doi.org/10.1007/s10565-012-9238-6 | DOI Listing |
Adv Healthc Mater
January 2025
Department of Clinical and Experimental Biomedical Sciences, University of Florence, Viale G.B. Morgagni, 50, Florence, 50134, Italy.
Mimicking compositions and structures of extracellular matrix is widely studied to create in vitro tumor models, to deepen the understanding of the pathogenesis of the different types of cancer, and to identify new therapies. On the other hand, the use of synthetic materials to modulate cancer cell biology and, possibly, to reduce the malignancy of cancer cells through their exploitation is far less explored. Here, the study evaluates the effects of Liquid Crystalline Networks (LCNs) based scaffolds on the growth of A375 metastatic melanoma cells.
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January 2025
Faculty of Medicine, Medical Biology Department, Bursa Uludag University, Bursa, Turkey.
The current study established the first in vitro Encorafenib resistance protocol in BRAF-mutated malignant melanoma (MM) cells and investigated the resistance-related mechanisms. After establishing Encorafenib-resistant A375-MM cells, resistant-related mechanisms were investigated using WST-1, Annexin V, cell cycle, morphological analysis, live-cell, Western blot, RNA-Seq, transmission electron microscopy-(TEM), oxidative stress and iron colorimetric assay. The most resistant group, called A375-R, was determined in the cells treated with a constant dose of 10 nM over 3 months.
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January 2025
Faculty of Computer and AI, Cairo University, Giza, Egypt.
Drug discovery and development is a challenging and time-consuming process. Laboratory experiments conducted on Vidarabine showed IC 6.97 µg∕mL, 25.
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January 2025
Dermatology, Changzhi Second People's Hospital, Changzhi, 046000, Shanxi, China.
The dysregulation of matrix metalloproteinases (MMPs) in skin cutaneous melanoma (SKCM) represents a critical aspect of tumorigenesis. In this study, we investigated the diagnostic, prognostic, and therapeutic aspects of the MMPs in SKCM. Thirteen SKCM cell lines and seven normal skin cell lines were cultured under standard conditions for experimental analyses.
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January 2025
Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA), 6th of October City, Egypt.
Nanotherapy has emerged as a promising strategy for the targeted and efficient treatment of melanoma, the most aggressive and lethal form of skin cancer, with minimized systemic toxicity. However, the therapeutic efficacy of cobalt oxide nanoparticles (CoONPs) in melanoma treatment remains unexplored. This study aimed to assess the therapeutic potential of CoONPs in melanoma treatment by evaluating their impact on cell viability, genomic DNA and mitochondrial integrity, reactive oxygen species (ROS) generation and apoptosis induction in melanoma A-375 cells.
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