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Article

Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma

1
Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country, 48940 Leioa, Bizkaia, Spain
2
Research and Development, Catalysis S.L., 28016 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Michele M. Iskandar
Nutrients 2021, 13(2), 686; https://doi.org/10.3390/nu13020686
Received: 31 December 2020 / Revised: 11 February 2021 / Accepted: 11 February 2021 / Published: 21 February 2021
(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)
Whereas the prevalence of several cancer types is decreasing, skin malignancies are growing more common every year. Malignant melanoma is the most aggressive form of skin cancer with high metastatic capacity. In most cases, malignant melanoma shows acquired therapy resistance. We evaluated the ability of Ocoxin, a natural compound-based antioxidant and anti-inflammatory nutritional complement, to exert an antitumor effect in melanoma. To do so, the cytotoxicity of Ocoxin in a panel of BRAF-mutated murine and human melanoma cell lines was tested alone and in combination with BRAF inhibitor Vemurafenib. Our results revealed a potent cytotoxic effect of Ocoxin against melanoma cells and a synergic effect when combined with Vemurafenib, reducing viability and increasing apoptosis. Besides, Ocoxin interferes with the cell cycle, impairs the inherent and fibroblast-mediated melanoma cell migration, and reduces resistance to BRAF inhibition. Proteomic analysis revealed reduced tumor secretion of inflammatory factors Galectin-1, Osteopontin, CCL5, and CCL9 upon treatment with Ocoxin. Moreover, RNASeq showed that Ocoxin downregulated the cell cycle and proliferation-related genes. In vivo, Ocoxin reduced the number of lung metastasis of YUMM-1.7 melanoma cells. Therefore, Ocoxin arises as a good candidate for clinical trials analyzing the beneficial effects in patients suffering from this cutaneous malignancy. View Full-Text
Keywords: melanoma; cancer nutrition; BRAF inhibition; fibroblasts; chemoresistance; adjuvant; tumor microenvironment melanoma; cancer nutrition; BRAF inhibition; fibroblasts; chemoresistance; adjuvant; tumor microenvironment
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MDPI and ACS Style

Benedicto, A.; Hernandez-Unzueta, I.; Sanz, E.; Márquez, J. Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma. Nutrients 2021, 13, 686. https://doi.org/10.3390/nu13020686

AMA Style

Benedicto A, Hernandez-Unzueta I, Sanz E, Márquez J. Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma. Nutrients. 2021; 13(2):686. https://doi.org/10.3390/nu13020686

Chicago/Turabian Style

Benedicto, Aitor, Iera Hernandez-Unzueta, Eduardo Sanz, and Joana Márquez. 2021. "Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma" Nutrients 13, no. 2: 686. https://doi.org/10.3390/nu13020686

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