Discovery of a new molecule inducing melanoma cell death: dual AMPK/MELK targeting for novel melanoma therapies. Academic Article uri icon

Overview

abstract

  • In the search of biguanide-derived molecules against melanoma, we have discovered and developed a series of bioactive products and identified the promising new compound CRO15. This molecule exerted anti-melanoma effects on cells lines and cells isolated from patients including the ones derived from tumors resistant to BRAF inhibitors. Moreover, CRO15 was able to decrease viability of cells lines from a broad range of cancer types. This compound acts by two distinct mechanisms. First by activating the AMPK pathway induced by a mitochondrial disorder. Second by inhibition of MELK kinase activity, which induces cell cycle arrest and activation of DNA damage repair pathways by p53 and REDD1 activation. All of these mechanisms activate autophagic and apoptotic processes resulting in melanoma cell death. The strong efficacy of CRO15 to reduce the growth of melanoma xenograft sensitive or resistant to BRAF inhibitors opens interesting perspective.

publication date

  • January 11, 2021

Research

keywords

  • AMP-Activated Protein Kinases
  • Melanoma
  • Protein Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC7801734

Scopus Document Identifier

  • 85099212118

Digital Object Identifier (DOI)

  • 10.1038/cdd.2010.75

PubMed ID

  • 33431809

Additional Document Info

volume

  • 12

issue

  • 1