title: Violacein, an indole-derived purple-colored natural pigment produced by Janthinobacterium lividum, inhibits the growth of head and neck carcinoma cell lines both in vitro and in vivo.
abstract: Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide. We determined whether VIO was able to inhibit head and neck cancer cell growth both in vitro and in vivo. We provide evidence that VIO treatment of human and mouse head and neck cancer cell lines inhibits cell growth and induces autophagy and apoptosis. In fact, VIO treatment increased PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of light chain 3-II (LC3-II). Moreover, VIO was able to induce p53 degradation, cytoplasmic nuclear factor kappa B (NF-κB) accumulation, and reactive oxygen species (ROS) production. VIO induced a significant increase in ROS production. VIO administration was safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) in vivo and prolonged median survival. Taken together, our results indicate that the treatment of head and neck cancer cells with VIO can be useful in inhibiting in vivo and in vitro cancer cell growth. VIO may represent a suitable tool for the local treatment of HNC in combination with standard therapies.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. laura.masuelli@uniroma1.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Masuelli
authors.affiliation: Department of Public Health and Infectious Diseases-Microbiology Section, Sapienza University of Rome, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pantanella
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Benvenuto
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fantini
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mattera
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Di Stefano
authors.affiliation: STA, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mattei
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, Rome, Italy.
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
authors.affiliation: Department of Public Health and Infectious Diseases-Microbiology Section, Sapienza University of Rome, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Schippa
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Manzari
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Modesti
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D042802:Oxalobacteraceae / Q000737:chemistry*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D000071137:Poly (ADP-Ribose) Polymerase-1; D020169:Caspases; C063155:violacein
keywords: Head and neck cancer; Janthinobacterium lividum; Violacein