title: In vitro anti-proliferation/cytotoxic activity of cantharidin (Spanish Fly) and related derivatives.
abstract: The anti-cancer therapeutic promise of cantharidin is limited because of its high mammalian toxicity. In order to find new anti-cancer lead compounds with reduced toxicity of the cantharidin prototype, the following seven derivatives were screened against the human SH-SY5Y neuroblastoma and MCF-7 breast cancer cells in vitro: 2,3-dimethyl-7-oxabicylo-[2.2.1]heptane-2,3-dicarboxylic anhydride (cantharidin) [1], 1-cyclohexen-1,2-dicarboxylic anhydride [2], cis-4-cyclohexen-1,2-dicarboxylic anhydride [3], cis-1, 2-cyclohexanedicarboxylic anhydride [4], exo-7-oxabicyclo[2.2.1]hept-5-ene-2-3 dicarboxylic anhydride [5], exo-7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride (norcantharidin) [6], and (S)-(-)-O-acetylmalic anhydride [7]. Cantharidin, was found to be the most effective anti-proliferative compound on both cell lines. However, on the human neuroblastoma cells cantharidin was of equal toxicity to compound [6]. Mode of action studies revealed that cantharidin inhibited growth factor-mediated activation of mitogen activated protein kinase (MAPkinase) and attenuated the de-phosphorylation of the extracellular regulated kinases 1 and 2 (erk1 and erk2).
authors.affiliation: Institutes of Bio-Organic Chemistry and Zoology, University of Hohenheim, Garbenstrasse 30, D-70593, Stuttgart, Germany. ladwill@uni-hohenheim.de
authors.forename: L A D
authors.initials: LA
authors.lastname: Williams
authors.forename: W
authors.initials: W
authors.lastname: Möller
authors.forename: E
authors.initials: E
authors.lastname: Merisor
authors.forename: W
authors.initials: W
authors.lastname: Kraus
authors.forename: H
authors.initials: H
authors.lastname: Rösner
mesh_terms: D000812:Anhydrides / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy; D002193:Cantharidin / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy; D014407:Tumor Cells, Cultured
chemical_list: D000812:Anhydrides; D004791:Enzyme Inhibitors; D016222:Fibroblast Growth Factor 2; D020928:Mitogen-Activated Protein Kinases; D002193:Cantharidin