Abstract
Microbial secondary metabolites have emerged as alternative novel drugs for the treatment of human cancers. Violacein, a purple pigment produced by Chromobacterium violaceum, was investigated in the present study for its anti-tumor properties in tumor cell lines. Clinically applicable concentrations of violacein were demonstrated to inhibit the proliferative capacity of tumor cell lines according to a crystal violet proliferation assay. The underlying mechanism was the promotion of apoptotic cell death, as indicated by poly(ADP ribose) polymerase cleavage and p44/42 mitogen-activated protein kinase signaling determined by western blot analysis. Collectively, this provided mechanistic evidence that violacein elicits extracellular-signal regulated kinase-induced apoptosis via the intrinsic pathway. The anti-malignant properties of violacein in the present study were further demonstrated by its inhibitory effects on brain tumor cell migration, specifically glioblastomas, one of the most invasive and therapeutically resistant neoplasms in the clinic. Additionally, solid tumors examined in the present study displayed differential cellular responses and sensitivities to violacein as observed by morphologically induced cellular changes that contributed to its anti-migratory properties. In conclusion, violacein is a novel natural product with the potential to kill several types of human tumor cell lines, as well as prevent disease recurrence by antagonizing cellular processes that contribute to metastatic invasion.
Highlights
The utility of bacteria as agents for the treatment of cancer was described over a century ago and continues to be investigated for their therapeutic value as delivery agents for anti‐cancer drugs and vectors for gene therapy [1,2,3]
The present study investigated a novel secondary metabolite, violacein, produced by a chromobacterium, for its utility as an agent that can promote tumor cell death in solid tumor‐derived cell lines
It was shown that violacein considerably reduced the proliferative capacity of lung and brain cancer cells, and to a much lesser extent that of breast cancer cells, providing an indication that cancers are differentially sensitive to this agent
Summary
The utility of bacteria as agents for the treatment of cancer was described over a century ago and continues to be investigated for their therapeutic value as delivery agents for anti‐cancer drugs and vectors for gene therapy [1,2,3]. Contemporary strategies have studied the use of bacterial products, including proteins, enzymes, immunotoxins and secondary metabolites for their anti‐tumor properties [1,2,3]. Violacein has been shown to have anti‐cancer properties in leukemia [23,24] and colon cancer cells [25,26,27], as well as in Ehrlich ascites tumors by Bromberg et al [28] using an in vivo mouse model In contrast to these studies, the present study used violacein extracted from a Chromobacterium violaceum strain native to a copper basin in Tennessee, which was demonstrated here to have anti‐proliferative effects on cell lines derived from solid tumors, as well as displayed an inhibitory effect on cancer cell migration, extending the anti‐tumorigenic properties of this bacterial‐produced metabolite
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