Merck
  • In Cellulo Evaluation of the Therapeutic Potential of NHC Platinum Compounds in Metastatic Cutaneous Melanoma.

In Cellulo Evaluation of the Therapeutic Potential of NHC Platinum Compounds in Metastatic Cutaneous Melanoma.

International journal of molecular sciences (2020-10-28)
Elsa Charignon, Mathilde Bouché, Caroline Clave-Darcissac, Georges Dahm, Gabriel Ichim, Anthony Clotagatide, Hichem C Mertani, Philippe Telouk, Julie Caramel, Jean-Jacques Diaz, Stéphane Bellemin-Laponnaz, Philippe Bouvet, Claire Billotey
摘要

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).

材料
货号
品牌
产品描述

Sigma-Aldrich
抗磷酸组蛋白H2A.X(Ser139)抗体,克隆JBW301, clone JBW301, Upstate®, from mouse
Sigma-Aldrich
Anti-FITC antibody, Mouse monoclonal, clone FL-D6, purified from hybridoma cell culture