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Title: Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE{sub 2} pathways in human M4Beu melanoma cancer cells

Abstract

Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide and is usually resistant to chemotherapy agents, which is due in part to a strong resistance to apoptosis. Previously, we had showed that B16-F0 murine melanoma cells undergoing apoptosis are able to delay their own death induced by ursolic acid (UA), a natural pentacyclic triterpenoid compound. We had demonstrated that tyrosinase and TRP-1 up-regulation in apoptotic cells and the subsequent production of melanin were implicated in an apoptosis resistance mechanism. Several resistance mechanisms to apoptosis have been characterized in melanoma such as hyperactivation of DNA repair mechanisms, drug efflux systems, and reinforcement of survival signals (PI3K/Akt, NF-κB and Raf/MAPK pathways). Otherwise, other mechanisms of apoptosis resistance involving different proteins, such as cyclooxygenase-2 (COX-2), have been described in many cancer types. By using a strategy of specific inhibition of each ways, we suggested that there was an interaction between melanogenesis and COX-2/PGE{sub 2} pathway. This was characterized by analyzing the COX-2 expression and activity, the expression of tyrosinase and melanin production. Furthermore, we showed that anti-proliferative and proapoptotic effects of UA were mediated through modulation of multiple signaling pathways including Akt and ERK-1/2 proteins. Ourmore » study not only uncovers underlying molecular mechanisms of UA action in human melanoma cancer cells but also suggest its great potential as an adjuvant in treatment and cancer prevention.« less

Authors:
;  [1];  [2]; ; ;  [1];  [3];  [1];  [1]
  1. Laboratory of Chemistry of Natural Substances, Faculty of Pharmacy, University of Limoges, FR 3503 GEIST, EA1069, Limoges (France)
  2. Laboratoire National de Référence (LNR), Université Mohammed VI des Sciences de la Santé, Casablanca (Morocco)
  3. Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences, Lebanese University, Beirut (Lebanon)
Publication Date:
OSTI Identifier:
22648587
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 345; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BORON 16; CHEMOTHERAPY; DEATH; DNA; DNA REPAIR; DRUGS; INHIBITION; MELANIN; MELANOMAS; MODULATION; TYROSINASE

Citation Formats

Hassan, Lama, Pinon, Aline, Limami, Youness, Seeman, Josiane, Fidanzi-Dugas, Chloe, Martin, Frederique, Badran, Bassam, Simon, Alain, and Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr. Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE{sub 2} pathways in human M4Beu melanoma cancer cells. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2016.05.023.
Hassan, Lama, Pinon, Aline, Limami, Youness, Seeman, Josiane, Fidanzi-Dugas, Chloe, Martin, Frederique, Badran, Bassam, Simon, Alain, & Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr. Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE{sub 2} pathways in human M4Beu melanoma cancer cells. United States. doi:10.1016/J.YEXCR.2016.05.023.
Hassan, Lama, Pinon, Aline, Limami, Youness, Seeman, Josiane, Fidanzi-Dugas, Chloe, Martin, Frederique, Badran, Bassam, Simon, Alain, and Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr. Fri . "Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE{sub 2} pathways in human M4Beu melanoma cancer cells". United States. doi:10.1016/J.YEXCR.2016.05.023.
@article{osti_22648587,
title = {Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE{sub 2} pathways in human M4Beu melanoma cancer cells},
author = {Hassan, Lama and Pinon, Aline and Limami, Youness and Seeman, Josiane and Fidanzi-Dugas, Chloe and Martin, Frederique and Badran, Bassam and Simon, Alain and Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr},
abstractNote = {Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide and is usually resistant to chemotherapy agents, which is due in part to a strong resistance to apoptosis. Previously, we had showed that B16-F0 murine melanoma cells undergoing apoptosis are able to delay their own death induced by ursolic acid (UA), a natural pentacyclic triterpenoid compound. We had demonstrated that tyrosinase and TRP-1 up-regulation in apoptotic cells and the subsequent production of melanin were implicated in an apoptosis resistance mechanism. Several resistance mechanisms to apoptosis have been characterized in melanoma such as hyperactivation of DNA repair mechanisms, drug efflux systems, and reinforcement of survival signals (PI3K/Akt, NF-κB and Raf/MAPK pathways). Otherwise, other mechanisms of apoptosis resistance involving different proteins, such as cyclooxygenase-2 (COX-2), have been described in many cancer types. By using a strategy of specific inhibition of each ways, we suggested that there was an interaction between melanogenesis and COX-2/PGE{sub 2} pathway. This was characterized by analyzing the COX-2 expression and activity, the expression of tyrosinase and melanin production. Furthermore, we showed that anti-proliferative and proapoptotic effects of UA were mediated through modulation of multiple signaling pathways including Akt and ERK-1/2 proteins. Our study not only uncovers underlying molecular mechanisms of UA action in human melanoma cancer cells but also suggest its great potential as an adjuvant in treatment and cancer prevention.},
doi = {10.1016/J.YEXCR.2016.05.023},
journal = {Experimental Cell Research},
number = 1,
volume = 345,
place = {United States},
year = {Fri Jul 01 00:00:00 EDT 2016},
month = {Fri Jul 01 00:00:00 EDT 2016}
}