Violacein negatively modulates the colorectal cancer survival and epithelial–mesenchymal transition

Abstract

Violacein is a secondary metabolite produced by several microorganisms including Chromobacterium violaceum, and it is already used in food and cosmetics. However, due to its potent anticancer and low side effects, its molecular action needs to be deeply scrutinized. Therefore, the main objective of this study was to evaluate the violacein's ability to interfere with three cancer hallmarks: growth factors receptor‐dependent signaling, proliferation, and epithelial–mesenchymal transition (EMT). Violacein has been associated with the induction of apoptosis in colorectal cancer (CRC) cells. Here, we demonstrate that this molecule is also active in CRC spheroids and inhibits cell migration. Violacein treatment reduced the amount of EGFR and AXL receptors in the HT29 cell line. Accordingly, the inhibition of the AKT, ERK, and PKCδ kinases, which are downstream mediators of the signaling pathways triggered by EGFR and AXL, is detected. Another interesting finding was that even when the cells were stimulated with transforming growth factor‐β, the EMT marker (N‐cadherin) decreased. Therefore, this study provides further evidence that reinforces the potential of violacein as an antitumor agent, once this biomolecule can “switch off” properties associated with cancer plasticity.

Violacein improves vemurafenib response in melanoma spheroids

“…The spheroids were obtained through Bio-Assembler n3D assay (Biosciences, Houston/TX) (de Souza Oliveira et al, 2022). Initially, the SK-MEL-28 were cultivated in a single layer (2D model) for 24h, then NanoShuttles TM (1µL/1x10 4 cells) were added to the culture medium upon the cells.…”

“…After the treatment with the ViVe protocol, the spheroids were washed with phosphate buffer solution (PBS) (100 µL/well) and fixed with Paraformaldehyde (PFA) 4% (100 µL/well) for 20 min. After the fixation, Calcein-AM (0.5 µL/1mL) and ethidium homodimer (2 µL/1mL) (Thermo Fisher Scientific) solutions were added (100 µL/well) as described by (de Souza Oliveira et al, 2022). The plate was incubated in a humidified atmosphere at 37 ºC and 5% CO2 for 1 h and then the fluorescence images were captured by LumaScope Ⓡ .…”