Chlorinated Guaiane-Type Sesquiterpene Lactones as Cytotoxic Agents against Human Tumor Cells.
Guaiane-type sesquiterpene lactones are naturally occurring compounds which have attracted attention due to their array of biological activities. In this study, chlorinated guaianolides 1-8, isolated from plants of the genus Centaurea, were evaluated against the human leukemia cell lines HL-60, U-937, a specific U-937 cell line that overexpresses the anti-apoptotic Bcl-2 protein and the human melanoma cell line SK-MEL-1. This established the relevant structure-growth inhibition relationships. Chlorohyssopifolins A (1), C (3) and D (4) and linichlorin A (6) were the most potent compounds in terms of inducing growth inhibition in the four cell lines. IC50 values were below 10 μM in all cases. Chlorohyssopifolins A (1) and D (4) and linichlorin A (6) were potent apoptotic inducers in human U-937 leukemia cells, as determined by fluorescent microscopy and flow cytometry, and their mechanism of action was associated with cytochrome c release, caspase activation and poly(ADP-ribose)polymerase cleavage. Overall this study shows that guaianolides induce cytotoxicity against human tumor cells and provides important insights into the cell death pathways that are involved.
['Estévez-Sarmiento|Francisco|F|', 'Saavedra|Ester|E|0000-0002-1717-386X', 'Ruiz-Estévez|Mercedes|M|', 'León|Francisco|F|0000-0002-5064-2381', 'Quintana|José|J|0000-0001-8225-4538', 'Brouard|Ignacio|I|', 'Estévez|Francisco|F|0000-0002-9728-2774']
D000970:Antineoplastic Agents D017209:Apoptosis D045304:Cytochromes c D003603:Cytotoxins D006801:Humans D007783:Lactones D007938:Leukemia D011065:Poly(ADP-ribose) Polymerases D045789:Sesquiterpenes, Guaiane D020298:U937 Cells
sesquiterpene lactone cytotoxicity guaianolide caspase apoptosis poly(ADP-ribose) polymerase