title: Pro-apoptotic activity of new analog of anthracyclines--WP 631 in advanced ovarian cancer cell line.
abstract: In this work we investigated the mode of cell death induced by WP 631, a novel anthracycline antibiotic, in the ovarian cancer cell line (OV-90) derived from the malignant ascites of a patient diagnosed with advanced disease. The effects were compared with those of doxorubicin (DOX), a first generation anthracycline. The ability of WP 631 to induce apoptosis and necrosis was examined by double staining with Annexin V and propidium iodide, measurements of the level of intracellular calcium ions and cytochrome c, PARP cleavage. We also investigated the possible involvement of the caspases activation, DNA degradation (comet assay) and intracellular reactive oxygen species (ROS) production in the development of the apoptotic events and their significance for drug efficiency. The results obtained clearly demonstrate that antiproliferative capacity of WP 631 in tested cell line was a few times greater than that of DOX. Furthermore, ovarian cancer cells treated with WP 631 showed a higher mean level of basal DNA damage in comparison to DOX. In conclusion, WP 631 is able to induce caspase - dependent apoptosis in human ovarian cancer cells. Obtained results suggested that WP 631 may be a candidate for further evaluation as chemotherapeutic agents for human cancers.
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. Electronic address: arekgajek86@wp.pl.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Gajek
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Denel
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bukowska
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Rogalska
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Marczak
mesh_terms: D018943:Anthracyclines / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010718:Phosphatidylserines / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; C104426:WP 631; D004317:Doxorubicin; D045304:Cytochromes c; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D002118:Calcium; D003630:Daunorubicin
keywords: Advanced ovarian cancer cells; Apoptosis; Caspases; DNA damage; WP 631