Discovery of a new molecule inducing melanoma cell death: dual AMPK/MELK targeting for novel melanoma therapies
| Autor: | Jaune, Emilie, Cavazza, Elisa, Ronco, Cyril, Grytsai, Oleksandr, Abbe, Patricia, Tekaya, Nedra, Zerhouni, Marwa, Beranger, Guillaume, Kaminski, Lisa, Bost, Frédéric, Gesson, Maeva, Tulic, Meri, Hofman, Paul, Ballotti, Robert, Passeron, Thierry, Botton, Thomas, Benhida, Rachid, Rocchi, Stéphane |
|---|---|
| Přispěvatelé: | Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Chimie de Nice (ICN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Hôpital Archet 2 [Nice] (CHU), Bost, Frédéric, Université Nice Sophia Antipolis (1965 - 2019) (UNS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell death
lcsh:Cytology [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] AMP-Activated Protein Kinases Protein Serine-Threonine Kinases Article [SDV.CAN] Life Sciences [q-bio]/Cancer [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Humans lcsh:QH573-671 Melanoma neoplasms Cell Proliferation Signal Transduction |
| Zdroj: | Cell Death and Disease Cell Death and Disease, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41419-020-03344-6⟩ Cell Death & Disease Cell Death and Disease, Vol 12, Iss 1, Pp 1-20 (2021) Cell Death and Disease, 2021, 12 (1), ⟨10.1038/s41419-020-03344-6⟩ |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-03344-6⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink