In vitro anticancer activity of prodeoxyviolacein produced by Yarrowia lipolytica through fermentation and predicted pharmacological properties compared with violacein derivatives.

Abstract

Microbial dyes, known for their biological activities, have been considered as an eco-friendly alternative to the toxic chemicals widely used in various industrial fields such as food, pharmaceuticals, textiles, and cosmetics. The green dye prodeoxyviolacein was produced by fermentation using an engineered strain of the yeast Yarrowia lipolytica, extracted using a mixture of ethanol/water/acetic acid. Prodeoxyviolacein showed an antiproliferative effect against MCF-7 cancer cell line. The apoptotic and cell cycle arresting capacities of the dye applied at the IC50 concentration were then assessed. Prodeoxyviolacein dye increased early cell apoptosis by arresting cell cycle at the sub-G1 phase. Violacein derivatives displayed comparable bioavailability characteristics. Derivatives had various predicted targets, among which kinases were the main common enzyme group. Docking studies showed prodeoxyviolacein to bind to the active site of tyrosine kinase and protein kinase C used as the main cancer therapeutic targets. Although structurally close, only prodeoxyviolacein displayed predicted blood-brain barrier penetrability due to its lower molecular weight and topological polar surface area. This fact might favor its use in the development of drugs to treat brain tumors. Prodeoxyviolacein is a new promising anticancer candidate with favorable pharmacokinetic properties.