Aloe-emodin exerts a potent anticancer and immunomodulatory activity on BRAF-mutated human melanoma cells

Ruggero De Maria Marchiano, Giovanni Sette, Claudio Tabolacci, Martina Cordella, Lorenzo Turcano, Stefania Rossi, Alessandro Lentini, Sabrina Mariotti, Roberto Nisini, Adriana Eramo, Lucia Piredda, Francesco Facchiano, Simone Beninati

Risultato della ricerca: Contributo in rivistaArticolo in rivista

30 Citazioni (Scopus)

Abstract

Aim of this study was to extend the knowledge on the antineoplastic effect of aloe-emodin (AE), a natural hydroxyanthraquinone compound, both in metastatic human melanoma cell lines and in primary stem-like cells (melanospheres). Treatment with AE caused reduction of cell proliferation and induction of SK-MEL-28 and A375 cells differentiation, characterized by a marked increase of transamidating activity of transglutaminase whose expression remained unmodified. In vitro antimetastatic property of AE was evaluated by adhesion and Boyden chamber invasion assays. The effect of AE on melanoma cytokines/chemokines production was determined by a multiplex assay: interestingly AE showed an immunomodulatory activity through GM-CSF and IFN-γ production. We report also that AE significantly reduced the proliferation, stemness and invasive potential of melanospheres. Moreover, AE treatment significantly enhanced dabrafenib (a BRAF inhibitor) antiproliferative activity in BRAF mutant cell lines. Our results confirm that AE possesses remarkable antineoplastic properties against melanoma cells, indicating this anthraquinone as a promising agent for differentiation therapy of cancer, or as adjuvant in chemotherapy and targeted therapy. Further, its mechanisms of action support a potential efficacy of AE treatment to counteract resistance of BRAF-mutated melanoma cells to target therapy.
Lingua originaleEnglish
pagine (da-a)283-292
Numero di pagine10
RivistaEuropean Journal of Pharmacology
Volume762
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • Aloe-emodin
  • Anthraquinones
  • Antineoplastic Agents
  • Apoptosis
  • BRAF-mutation
  • Cell Adhesion
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytokines
  • Drug Synergism
  • Humans
  • Imidazoles
  • Immunologic Factors
  • Medicine (all)
  • Melanoma
  • Melanoma cell differentiation
  • Melanoma-initiating cells
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Oximes
  • Pharmacology
  • Proto-Oncogene Proteins B-raf

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