Biochemistry & Pharmacology: Open Access
Open Access
ISSN: 2167-0501
ISSN: 2167-0501
Pedro Buc Calderon
Accepted Abstracts: Biochem & Pharmacol
Juglone (5-hydroxy-1,4-naphthoquinone), occurs naturally in the leaves, roots, husks, and bark of plants in the Juglandaceae family, particularly the black walnut ( Juglans nigra ), and is toxic to some plants and insect herbivores as well. Like several naphthoquinones, the antitumor activity of Juglone relies on a quinone redox cycling capacity that triggers oxidative stress. Such a quinone redox cycling is strongly enhanced by vitamin C, a natural reducing agent. Since cancer cells are highly sensitive to an oxidative stress, the effects of jugloneon T24 bladder cancer cells either in the absence or in the presence of sodium ascorbate (vitamin C) were investigated.The end-points used to characterize the juglone-mediated cytotoxicity, included cell functionality (MTT assay and cell morphology), formation of reactive oxygen species (ROS), GSH levels, caspase-3 activity, PARP cleavage and protein phosphorylation of histone H2AX and eukaryotic initiation factor 2 (eIF2 α ). Cell proliferation and motility were monitored by the colony forming and the wound healing assays. The EC 50 value at 24 h for juglone was 5-fold decreased in the presence of ascorbate. Juglone alone or associated with ascorbate neither cause caspase-3 activation nor PARP cleavage, indicating that cell demise is rather necrotic than apoptosis. In cells treated by juglone, a concentration-dependent decrease in cell proliferation was observed. Ascorbate did not impair the capacity of cells to proliferate, but its association with juglone leads to a clonogenic death state and impairment of cell migration. In summary, juglone causes clonogenic death, inhibiting proliferation and motility of T24 cells. These effects were enhanced by ascorbate.
Pedro Buc Calderongot his Ph.D. at the Universit� catholique de Louvain (UCL), Belgium. He is Professor of Toxicology and director of the research group on Toxicology and Cancer Biology (UCL). He has published over 100 articles and has been serving as an editorial board member. He has directed 12 doctoral theses. He has been invited as a speaker to various international conferences. His research is focused in the study of molecular mechanisms inducing cancer cell death. He is now studying natural products isolated from plants of the North Chilean desert as chemotherapeutic agents.