Zeaxanthin from Porphyridium purpureum induces apoptosis in human melanoma cells expressing the oncogenic BRAF V600E mutation and sensitizes them to the BRAF inhibitor vemurafenib

Abstract

Zeaxanthin, an abundant carotenoid present in fruits, vegetables and algae was reported to exert antiproliferative activity and induce apoptosis in human uveal melanoma cells. It also inhibited uveal melanoma tumor growth and cell migration in nude mice xenograft models. Here we report that zeaxanthin purified from the rhodophyte Porphyridium purpureum (Bory) K.M.Drew & R.Ross, Porphyridiaceae, promotes apoptosis in the A2058 human melanoma cell line expressing the oncogenic BRAF V600E mutation. Zeaxanthin 40 μM (IC50) induced chromatin condensation, nuclear blebbing, hypodiploidy, accumulation of cells in sub-G1 phase, DNA internucleosomal fragmentation and activation of caspase-3. Western blot analysis revealed that zeaxanthin induced up-regulation of the pro-apoptotic factors Bim and Bid and inhibition of NF-κB transactivation. Additionally, zeaxanthin sensitized A2058 melanoma cells in vitro to the cytotoxic activity of vemurafenib, a BRAF inhibitor widely used for the clinical management of melanoma, suggesting its potential interest as dietary adjuvant increasing melanoma cells sensitivity to chemotherapy.

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Correspondence to Laurent Picot.

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JBB and EN produced P. purpureum biomass. CJ, RGOJ, AF, CO, LPy,IL, GP and LP performed the pigment extraction, purification, cell culture, western-blot and apoptosis experiments. CJ performed the HRMS analysis. LB and CJ performed the flux cytometry analysis. LP designed the experiments, interpreted the data, directed the study and wrote the manuscript in collaboration with VT and JRGDSA. LP takes responsibility for the integrity of the work, from inception to finished article.

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Juin, C., de Oliveira Junior, R.G., Fleury, A. et al. Zeaxanthin from Porphyridium purpureum induces apoptosis in human melanoma cells expressing the oncogenic BRAF V600E mutation and sensitizes them to the BRAF inhibitor vemurafenib. Rev. Bras. Farmacogn. 28, 457–467 (2018). https://doi.org/10.1016/j.bjp.2018.05.009

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Keywords

  • Cancer
  • Carotenoid
  • Melanoma
  • Microalgae
  • Phytoplankton
  • Zeaxanthin