Natural products have been shown to serve as promising starting points for novel anti cancer drugs. In this study, the anti-cancer activities of the purple compound violacein,
initially isolated from Chromobacterium violaceum, were investigated. To highlight the
crucial role of the tumor microenvironment on the effectiveness of cancer therapies, this
study includes effects on macrophages as prototypic cells of the microenvironment in
addition to the investigation of tumor-centric activities. Using 2D and 3D cell culture
models, automated live-cell microscopy, and biochemical analyses, violacein was
demonstrated to inhibit tumor cell proliferation and migration. The violacein-triggered
tumor cell death was further associated with caspase 3-like activation and ATP release.
Stimuli released from dead cells resulted in inflammatory activation of macrophages, as
shown by NF-kB reporter cell assays, macrophage morphology, and gene expression
analysis. Moreover, macrophages deficient in the inflammasome component Nlrp3 were
found to be significantly less sensitive towards treatment with violacein and doxorubicin.
Taken together, this study provides new insights into the biological activity of violacein
against cancer. In addition, the in vitro data suggest immunogenic features of induced cell
death, making violacein an interesting candidate for further studies investigating the
compound as an inducer of immunogenic cell death