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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)283-292
Number of pages10
JournalEuropean Journal of Pharmacology
Volume762
DOIs
Publication statusPublished - Jun 12 2015

Fingerprint

Melanoma
Antineoplastic Agents
Therapeutics
aloe emodin
Cell Line
Anthraquinones
Transglutaminases
Adjuvant Chemotherapy
Granulocyte-Macrophage Colony-Stimulating Factor
Chemokines
Cell Differentiation
Stem Cells
Cell Proliferation
Cytokines
Neoplasms

Keywords

  • Aloe-emodin
  • BRAF-mutation
  • Cytokines
  • Melanoma cell differentiation
  • Melanoma-initiating cells

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tabolacci, C., Cordella, M., Turcano, L., Rossi, S., Lentini, A., Mariotti, S., ... Beninati, S. (2015). Aloe-emodin exerts a potent anticancer and immunomodulatory activity on BRAF-mutated human melanoma cells. European Journal of Pharmacology, 762, 283-292. https://doi.org/10.1016/j.ejphar.2015.05.057

Aloe-emodin exerts a potent anticancer and immunomodulatory activity on BRAF-mutated human melanoma cells. / Tabolacci, Claudio; Cordella, Martina; Turcano, Lorenzo; Rossi, Stefania; Lentini, Alessandro; Mariotti, Sabrina; Nisini, Roberto; Sette, Giovanni; Eramo, Adriana; Piredda, Lucia; De Maria, Ruggero; Facchiano, Francesco; Beninati, Simone.

In: European Journal of Pharmacology, Vol. 762, 12.06.2015, p. 283-292.

Research output: Contribution to journalArticle

Tabolacci, C, Cordella, M, Turcano, L, Rossi, S, Lentini, A, Mariotti, S, Nisini, R, Sette, G, Eramo, A, Piredda, L, De Maria, R, Facchiano, F & Beninati, S 2015, 'Aloe-emodin exerts a potent anticancer and immunomodulatory activity on BRAF-mutated human melanoma cells', European Journal of Pharmacology, vol. 762, pp. 283-292. https://doi.org/10.1016/j.ejphar.2015.05.057
Tabolacci, Claudio ; Cordella, Martina ; Turcano, Lorenzo ; Rossi, Stefania ; Lentini, Alessandro ; Mariotti, Sabrina ; Nisini, Roberto ; Sette, Giovanni ; Eramo, Adriana ; Piredda, Lucia ; De Maria, Ruggero ; Facchiano, Francesco ; Beninati, Simone. / Aloe-emodin exerts a potent anticancer and immunomodulatory activity on BRAF-mutated human melanoma cells. In: European Journal of Pharmacology. 2015 ; Vol. 762. pp. 283-292.
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