title: Cyclic versus hemi-bastadins. pleiotropic anti-cancer effects: from apoptosis to anti-angiogenic and anti-migratory effects.
abstract: Bastadins-6, -9 and -16 isolated from the marine sponge Ianthella basta displayed in vitro cytostatic and/or cytotoxic effects in six human and mouse cancer cell lines. The in vitro growth inhibitory effects of these bastadins were similar in cancer cell lines sensitive to pro-apoptotic stimuli versus cancer cell lines displaying various levels of resistance to pro-apoptotic stimuli. While about ten times less toxic than the natural cyclic bastadins, the synthetically derived 5,5'-dibromohemibastadin-1 (DBHB) displayed not only in vitro growth inhibitory activity in cancer cells but also anti-angiogenic properties. At a concentration of one tenth of its in vitro growth inhibitory concentration, DBHB displayed actual antimigratory effects in mouse B16F10 melanoma cells without any sign of cytotoxicity and/or growth inhibition. The serum concentration used in the cell culture media markedly influenced the DBHB-induced antimigratory effects in the B16F10 melanoma cell population. We are currently developing a specific inhalation formulation for DBHB enabling this compound to avoid plasmatic albumin binding through its direct delivery to the lungs to combat primary as well as secondary (metastases) tumors.
authors.affiliation: Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Campus de la Plaine, Boulevard du Triomphe, 1050 Brussels, Belgium. vemathie@ulb.ac.be
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wauthoz
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.forename: Hendrik
authors.initials: H
authors.lastname: Niemann
authors.forename: Karim
authors.initials: K
authors.lastname: Amighi
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology* / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011161:Porifera / Q000737:chemistry; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D055768:Halogenated Diphenyl Ethers; D012709:Serum Albumin; C583171:bastadin 16; C515158:bastadin 6; C068507:bastadin 9