Carotenoids from Rhodomonas salina Induce Apoptosis and Sensitize A2058 Melanoma Cells to Chemotherapy

Abstract

Melanoma is an aggressive tumor with invasive and metastatic potential, frequently exhibiting multidrug resistance mechanisms. In our continuous search for antimelanoma molecules, we have identified some effective marine compounds capable of not only inducing cell death, but also of sensitizing chemoresistant tumor cells to clinically used anticancer drugs. In this report, the cryptophyte Rhodomonas salina (Wislouch) D.R.A.Hill & R.Wetherbee, Pyrenomonadaceae, was chemically investigated in order to identify pigments efficiently inhibiting melanoma cells proliferation. All pharmacological tests were performed on A2058 cells expressing the oncogenic BRAF V600E mutation and resistant to dacarbazine treatment. Flash chromatography of R. salina ethanol extract led to purification of alloxanthin and crocoxanthin, which showed significant antiproliferative activity against A2058 cells, exhibiting IC50 = 29 and 50 μM, respectively. These carotenoids promoted growth inhibition, decreased cell migration, and induced apoptosis and sub-G1 cells accumulation after 72 h of treatment. In addition, alloxanthin potentiated the cytotoxic activity of vemurafenib (a BRAF inhibitor) and restored the sensitivity of A2058 cells to dacarbazine treatment.

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Acknowledgments

We thank Thierry Beignon from Synoxis Algae Company (Le Cellier, France) for the loan of LUCY photobioreactor.

Funding

This research was financially supported by the INTERREG Atlantic Area European program (Interreg EnhanceMicroAlgae project, EAPA_338/2016), and the French cancer league (Comité 17 de la Ligue Nationale contre le Cancer).

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EN produced R. salina biomass; RGOJ and AB performed pigments extraction, purification and characterization by UPLC-DAD-MS/MS analysis; RGOJ, GP, LB and LP performed all pharmacological tests (cell culture, fluorescence microscopy, live cell imaging, flow cytometry, etc.); RGOJ and NJ performed SEM analysis; RGOJ and VT participated in the design of the manuscript, data analysis and interpretation and in the writing process; LP supervised the entire study in collaboration with VT and EN.

Corresponding author

Correspondence to Laurent Picot.

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de Oliveira-Júnior, R.G., Nicolau, E., Bonnet, A. et al. Carotenoids from Rhodomonas salina Induce Apoptosis and Sensitize A2058 Melanoma Cells to Chemotherapy. Rev. Bras. Farmacogn. 30, 155–168 (2020). https://doi.org/10.1007/s43450-020-00036-2

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Keywords

  • Alloxanthin
  • Chemosensitivity
  • Crocoxanthin
  • Cutaneous melanoma
  • Drug resistance
  • Microalgae