title: Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety.
abstract: A combination of demethylcantharidin, a modified component of a traditional Chinese medicine (TCM), with a platinum moiety has produced a series of TCM-based platinum compounds [Pt(C(8)H(8)O(5))(NH(2)R)(2)] 1-5, which demonstrate selective cytotoxicity toward SK-Hep-1 (human liver) cell line, and circumvention of cross-resistance. The inclusion of demethylcantharidin rendered the compounds highly active as protein phosphatase (PP2A) inhibitors. The new TCM-Pt compounds may possess a novel dual mechanism of antitumor action: inhibition of PP2A and platination of DNA.
authors.affiliation: School of Pharmacy, Department of Pharmacology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, The People's Republic of China. yeepingho@cuhk.edu.hk
authors.forename: Y P
authors.initials: YP
authors.lastname: Ho
authors.forename: K K
authors.initials: KK
authors.lastname: To
authors.forename: S C
authors.initials: SC
authors.lastname: Au-Yeung
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Lin
authors.forename: X
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000627:therapeutic use; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D009944:Organoplatinum Compounds; C069741:norcantharidin; D010749:Phosphoprotein Phosphatases