Violacein improves vemurafenib response in melanoma spheroids

Author(s)

Aires-Lopes, Beatriz ; Justo, Giselle Zenker ; Cordeiro, Helon Guimaraes ; Duran, N. ; Azevedo-Martins, Jordana Maria ; Halder, Carmen Verissima Ferreira

• Document type: Journal article
• Source: NATURAL PRODUCT RESEARCH; v. N/A, p. 4-pg., 2023-08-02.

Abstract

Chemotherapy resistance is one of the main challenges in melanoma treatment. Violacein, a natural pigment produced by Chromobacterium violaceum, induces apoptosis in a variety of tumours, including melanoma. Here, we used BRAF-mutated melanoma spheroids to test the potential of violacein as a sensitizer of cellular viability and levels of the proteins p62 and fatty acid synthase (FASN). Importantly, violacein in combination with vemurafenib (ViVe) was able to interfere with spheroid survival at subtoxic concentrations. The results demonstrated that the ViVe protocol triggered cell death assessed by calcein and ethidium homodimer dyes. Accordingly, melanoma cells in 2D systems also showed a higher apoptosis rate when treated with ViVe. In the current study, we show evidence that ViVe downregulates crucial mediators like FASN, which partially explains how it acts as a sensitizer and ultimately improves the effectiveness of vemurafenib against melanoma cells. (AU)

• FAPESP's process: 20/12828-7 - Biomarkers of autophagy and fatty acid synthesis: tracking the response of melanoma spheroids to the drug holiday therapeutic regimen
• Grantee: Beatriz Aires Lopes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation