title: Induction of apoptosis on carcinoma cells by two synthetic cantharidin analogues.
abstract: Cantharidin isolated from Mylabris caraganae and other insects has been used as an anti-cancer drug in China for many years. However, its toxicity on the renal system and suppression effect on bone marrow limits its usage clinically. Based on the core structure of cantharidin, we have chemically synthesized two cantharidin analogues (compounds 2 and 3). The cytotoxic activity of these analogues was demonstrated on the Hep3B hepatocellular carcinoma, MDA-MB231 breast cancer, A549 non-small cell lung carcinoma and KG1a acute myelogenous leukaemia (AML) cell lines by monitoring the intracellular adenosine triphosphate level. Morphological changes in these cancer cell lines, including cell shrinkage and loss of adherent potential, were readily observed. By making use of the KG1a AML cells as a test model, we further found that mitochondrial membrane potential depolarization and reduction of intracellular bcl-2 anti-apoptotic protein level were involved. These resulted in the activation of caspase 3 protease activity and oligonucleosomal length DNA fragment formation as detected by both time resolved fluorescence technology-based caspase activity assay and TdT-mediated dUTP nick end-labelling assay.
authors.affiliation: Anti-cancer Research Center, Shenzhen Key Laboratory of Chinese Medicine and Molecular Pharmacology and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, P.R. China.
authors.forename: Stanton Hon Lung
authors.initials: SH
authors.lastname: Kok
authors.forename: Chung Hin
authors.initials: CH
authors.lastname: Chui
authors.forename: Wing Sze
authors.initials: WS
authors.lastname: Lam
authors.forename: Jien
authors.initials: J
authors.lastname: Chen
authors.forename: Johnny Cheuk On
authors.initials: JC
authors.lastname: Tang
authors.forename: Fung Yi
authors.initials: FY
authors.lastname: Lau
authors.forename: Gregory Yin Ming
authors.initials: GY
authors.lastname: Cheng
authors.forename: Raymond Siu Ming
authors.initials: RS
authors.lastname: Wong
authors.forename: Albert Sun Chi
authors.initials: AS
authors.lastname: Chan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002193:Cantharidin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects*; D048430:Cell Shape; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008928:Mitochondria / Q000378:metabolism; D015394:Molecular Structure
chemical_list: D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002193:Cantharidin