Violacein induces p44/42 mitogen-activated protein kinase-mediated solid tumor cell death and inhibits tumor cell migration

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.

Advances in Chromobacterium violaceum and properties of violacein-Its main secondary metabolite: A review

“…Of importance, reduction in glioblastoma migration induced by violacein without affecting adhesion was shown. This activity was attributed to the ability of violacein to disrupt the actin network, thus interfering with cell morphology and motility (Mehta et al, 2015). This study reinforced the previous work published by Platt et al (2014) on the activity of violacein to prevent cancer metastasis.…”

“…Thus, these findings open new possibilities to explore violacein as a novel compound to improve anticancer treatment by acting on the communication of tumor cells with their surrounding microenvironment. Mehta et al (2015) recently reported the cytotoxicity and mechanisms of action of violacein in three different cells lines, namely glioblastoma (U87), breast cancer (MCF7) and lung cancer (A549). Breast and lung cancers are two of the most common cancer types in men and women, frequently showing a high incidence of brain metastasis.…”

Antineoplastic potential and chemical evaluation of essential oils from leaves and flowers of Tagetes ostenii Hicken

“…For the treatment with EO 1, this process appears not to be affected after 48 h. During metastasis, abnormal cells with genomic heterogeneity may undergo epithelial-to-mesenchymal transition (EMT) and phenotypically exhibit increased motility and invasiveness as compared to normal cells (Pavelic et al 2011). The ability to form solid tumors, like cervical cancer, is also affected by the reduction of cell migration as reported by (Mehta et al 2015).…”

The Effect of Onosma bracteatum in cancer cells

“…7 The finding from this study observed the anti-proliferative activity of O. bracteatum on A549 lung cancer cell line, BT549 breast cancer cell line, and PC3 prostate cancer cell line. 8 Also, there was an effect of O. bracteatum on Lipid Peroxidase Level in lung cancer (A549), breast cancer (BT549), and prostate cancer (PC3) cells, and the activation of Caspase-3 by O. bracteatum was evaluated. We have conducted series of assays like cell viability/ proliferation, effect on cell ROS generation, and cell apoptosis or assessing the effect of O. bracteatum against the selected A549 lung cancer, BT549 breast cancer, and PC3 prostate cancer cells.…”