Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment

Abstract

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-κB 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.

Multi-omics analysis reveals the impact of intratumor microbes on lung adenocarcinoma prognosis and ICB treatment

“…7B). Previous studies have indicated that chromobacterium, which is enriched in R,can potentially induce infections, and its main metabolite,violacein,holds promise as a therapeutic agent against cancer [34].Interestingly, this microbiota was also enriched in the ICI-3 subtype.On the other hand, Lachnoclostridium,which was found to be enriched in NR,has been reported to modulate the response to ICB treatment in patients with hepatocellular carcinoma [35].Considering the potential interaction between microbiota-ICB response association and genetic or other environmental factors,we conducted cluster analysis.The results revealed greater microbiota differences between NR and R groups in the ICI-1 subtype compared to the ICI-3 subtype(Fig. 7C).…”

Priming Chromobacterium violaceum as a Gold Bioleacher in E-wastes: Advantages and Challenges

“…to protect itself against competing bac-teria [72,73], fungi [74], and viruses [75]. Besides, violacein has also been demonstrated to be an effective anticancer [76] and immunomodulatory compound [77], two important characteristics for successful cancer treatment. Hence, it may be advantageous to use violacein derived from Chromobacterum spp.…”

Synthetic co-culture in an interconnected two-compartment bioreactor system: violacein production with recombinant E. coli strains

“…The natural secondary metabolite violacein (VIO) and its derivatives demonstrate striking pharmacological properties against Methicillin-resistant Staphylococcus aureus strains [ 1 ], malaria parasites [ 2 , 3 ], and viral pathogens [ 4 , 5 ] amongst others. Moreover, the versatile functions of VIO also include the potential to induce tumor cell death [ 6 , 7 ] or enhance antibody production in Chinese hamster ovary cells [ 8 ], suggesting an even wider range of applications in healthcare and pharmaceutical industries. Additionally, the UV-absorbing and dyeing properties of the natural pigment in combination with its antibiotic properties may lead to potential applications in the fields of cosmetic and textile production [ 9 , 10 ].…”