Molecular mechanism of violacein-mediated solid tumor death and its anti-migratory properties

Patients with developed solid tumors can resist conventional anticancer therapies, which have provoked the need for alternative cancer therapies. Successful novel anticancer therapies depend on their selectivity for cancer cells with limited toxicity to normal tissue. For the progressive decline of specific forms of cancer, the use of bacteria has been recognized for more than a century. Products derived from bacteria such as cytotoxic factors, enzymes, antibiotics and other secondary metabolites have been tested and successfully used for this purpose. A secondary metabolite, violacein, was extracted from Chromobacterium violaceum 14N23 strain isolated from Copper Basin, Tennessee, for studying its anti-tumor activities in solid tumors. Violacein was extracted and purified by modifying the technique of Rettori and Duran (1998) after which it was analyzed and identified by mass spectrometry, UV-VIS spectroscopy and HPLC (High-Performance Liquid Chromatography). Different doses of violacein were examined in brain (U87), lung (A549) and breast (MCF7) cancer cell lines to assess the suitability of violacein as a chemotherapeutic agent. Several studies have shown that violacein is capable of inducing apoptosis in various cancer cells. Herein, we studied the underlying mechanism of violacein cytotoxicity, which was preceded by activation of poly (ADP-ribose) polymerase cleavage and p44/42 mitogen-activated protein kinase signaling, which was the promotion of apoptotic cell death. This result provided us with the mechanistic information that violacein provoked extracellular-signal regulated kinase-induced apoptosis via the intrinsic pathway. Further in the present study, anti-malignant properties of violacein were investigated in brain tumors by studying inhibitory effects of violacein on cell migration. Brain tumors, specifically glioblastomas, were chosen because they are one of the most invasive and therapeutically resistant neoplasms. Also, cancer cell lines studied were sensitive to violacein, which was observed by morphologically induced cellular changes. All the results acquired suggest that violacein is a novel natural product with the aptitude to kill several types of human tumor cell lines