In Cellulo Evaluation of the Therapeutic Potential of NHC Platinum Compounds in Metastatic Cutaneous Melanoma.
Antineoplastic Agents
/ chemistry
Cell Death
/ drug effects
Cell Line, Tumor
Cell Survival
/ drug effects
DNA Breaks, Double-Stranded
/ drug effects
DNA Damage
Drug Resistance, Neoplasm
/ drug effects
Drug Screening Assays, Antitumor
Heterocyclic Compounds
/ chemistry
Humans
Melanoma
/ drug therapy
Methane
/ analogs & derivatives
Organoplatinum Compounds
/ chemistry
Proto-Oncogene Proteins B-raf
/ antagonists & inhibitors
Skin Neoplasms
/ drug therapy
bcl-X Protein
/ metabolism
Melanoma, Cutaneous Malignant
BRAF inhibitor resistance
apoptosis
chemoresistance
chemotherapy
metastatic cutaneous melanoma
platinum N-heterocyclic carbene complexes
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
22 Oct 2020
22 Oct 2020
Historique:
received:
07
09
2020
revised:
08
10
2020
accepted:
19
10
2020
entrez:
27
10
2020
pubmed:
28
10
2020
medline:
22
4
2021
Statut:
epublish
Résumé
We describe here the evaluation of the cytotoxic efficacy of two platinum (II) complexes bearing an N-heterocyclic carbene (NHC) ligand, a pyridine ligand and bromide or iodide ligands on a panel of human metastatic cutaneous melanoma cell lines representing different genetic subsets including BRAF-inhibitor-resistant cell lines, namely A375, SK-MEL-28, MeWo, HMCB, A375-R, SK-MEL-5-R and 501MEL-R. Cisplatin and dacarbazine were also studied for comparison purposes. Remarkably, the iodine-labelled Pt-NHC complex strongly inhibited proliferation of all tested melanoma cells after 1-h exposure, likely due to its rapid uptake by melanoma cells. The mechanism of this inhibitory activity involves the formation of DNA double-strand breaks and apoptosis. Considering the intrinsic chemoresistance of metastatic melanoma cells of current systemic treatments, these findings are promising and could give research opportunities in the future to improve the prognosis of patients suffering from unresectable metastatic melanoma that are not eligible or that do not respond to the most effective drugs available to date, namely BRAF inhibitors and the anti-PD-1 monoclonal antibody (mAb).
Identifiants
pubmed: 33105692
pii: ijms21217826
doi: 10.3390/ijms21217826
pmc: PMC7659946
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
BCL2L1 protein, human
0
Heterocyclic Compounds
0
Organoplatinum Compounds
0
bcl-X Protein
0
carbene
2465-56-7
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Methane
OP0UW79H66
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : La ligue contre le cancer
ID : CCIR Est
Organisme : Idex Université de Strasbourg
ID : Programme interdisciplnaire
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