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

Type Article
Date 2018-07
Language English
Author(s) Juin Camille1, De Oliveira Junior Raimundo Gonsalves1, 3, Fleury Audrey1, Oudinet Chloe1, Pytowski Lior1, Berard Jean-BaptisteORCID2, Nicolau ElodieORCID2, Thiery Valerie1, Lanneluc Isabelle1, Beaugeard Laureen1, Prunier Gregoire1, Guedes Da Silva Almeida Jackson Roberto3, Picot Laurent1
Affiliation(s) 1 : Univ La Rochelle, CNRS, Littoral Environm & Soc UMR 7266, La Rochelle, France.
2 : Inst Francais Rech Exploitat Mer, Lab Physiol & Biotechnol Algues, Lab Biotechnol & Ressources Marines, Nantes, France.
3 : Fed Univ San Francisco Valley, Ctr Studies & Res Med Plants, Petrolina, PE, Brazil.
Source Revista Brasileira De Farmacognosia-brazilian Journal Of Pharmacognosy (0102-695X) (Soc Brasileira Farmacognosia), 2018-07 , Vol. 28 , N. 4 , P. 457-467
DOI 10.1016/j.bjp.2018.05.009
WOS© Times Cited 1
Keyword(s) Cancer, Carotenoid, Melanoma, Microalgae, Phytoplankton, Zeaxanthin
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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Juin Camille, De Oliveira Junior Raimundo Gonsalves, Fleury Audrey, Oudinet Chloe, Pytowski Lior, Berard Jean-Baptiste, Nicolau Elodie, Thiery Valerie, Lanneluc Isabelle, Beaugeard Laureen, Prunier Gregoire, Guedes Da Silva Almeida Jackson Roberto, Picot Laurent (2018). Zeaxanthin from Porphyridium purpureum induces apoptosis in human melanoma cells expressing the oncogenic BRAF V600E mutation and sensitizes them to the BRAF inhibitor vemurafenib. Revista Brasileira De Farmacognosia-brazilian Journal Of Pharmacognosy, 28(4), 457-467. Publisher's official version : https://doi.org/10.1016/j.bjp.2018.05.009 , Open Access version : https://archimer.ifremer.fr/doc/00444/55595/