The Nitrobenzoxadiazole Derivative MC3181 Blocks Melanoma Invasion and Metastasis

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Jan 21

PMID 28107182

Citations 11

Authors

Anastasia De Luca

Debora Carpanese

Maria Cristina Rapanotti

Tara Mayte Suarez Viguria

Maria Antonietta Forgione

Dante Rotili

Chiara Fulci

Egidio Iorio

Luigi Quintieri

Sergio Chimenti

Luca Bianchi

Antonio Rosato

Anna Maria Caccuri

Affiliations

Soon will be listed here.

Abstract

The novel nitrobenzoxadiazole (NBD) derivative MC3181 is endowed with remarkable therapeutic activity in mice bearing both sensitive and vemurafenib-resistant human melanoma xenografts. Here, we report that subtoxic concentrations of this compound significantly reduced invasiveness of BRAF-V600D mutated WM115 and WM266.4 melanoma cell lines derived from the primary lesion and related skin metastasis of the same patient, respectively. The strong antimetastatic activity of MC3181 was observed in both 2D monolayer cultures and 3D multicellular tumor spheroids, and confirmed in vivo by the significant decrease in the number of B16-F10 melanoma lung metastases in drug-treated mice. Our data also show that MC3181 affects the lactate production in the high glycolytic WM266.4 cell line. To unveil the MC3181 mechanism of action, we analyzed the ability of MC3181 to affect the degree of activation of different MAPK pathways, as well as the expression/activity levels of several proteins involved in angiogenesis, invasion, and survival (i.e. AP2, MCAM/MUC18, N-cadherin, VEGF and MMP-2). Our data disclosed both a decrease of the phospho-active form of JNK and an increased expression of the transcription factor AP2, events that occur in the very early phase of drug treatment and may be responsible of the antimetastatic effects of MC3181.

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