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Title: Apoptotic activity of a novel synthetic cantharidin analogue on hepatoma cell lines
Authors: Kok, SHL
Chui, CH
Lam, WS
Chen, J
Lau, FY
Cheng, GYM
Wong, RSM
Lai, PPS
Leung, TWT
Tang, JCO 
Chan, ASC
Keywords: Apoptosis
Issue Date: 2006
Publisher: Spandidos Publications
Source: International journal of molecular medicine, 2006, v. 17, no. 5, p. 945-949 How to cite?
Journal: International journal of molecular medicine 
Abstract: Cantharidin isolated from Mylabris caraganae and other insects is used traditionally as an anti-cancer drug. However, its toxicity on the renal system and suppression effect on bone marrow limits its clinical usage. Recently, we have synthesized two cantharidin analogues, CAN 029 (compound 2) and CAN 030 (compound 3). Although both showed an apoptotic induction ability on cancer cells, they were still relatively toxic towards non-malignant haematological disordered bone marrow. Based on the principle structure of cantharidin, we have further chemically synthesized another analogue, CAN 032. The cytotoxic activity of this analogue was screened on both Hep3B hepatocellular carcinoma and SK-Hep-1 liver adenocarcinoma cell lines by [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] (MTS) assay. Morphological changes of hepatoma cell lines were recorded under an inverted microscope. The possible tolerance of these analogues was further investigated using non-malignant haematological bone marrow primary culture. CAN 032 showed a significant cytotoxic response on both hepatoma cell lines in which the potencies were comparable to that of cantharidin. Further screening on the bone marrow tolerance revealed that compound CAN 032 showed a relatively less toxic effect. Phase contrast microscopy demonstrated that cell shrinkage, rounding, loss of adherent property and loss of colony-formation ability were induced. The dose-dependence of the response of CAN 032 on Hep3B was further assayed by DNA fragmentation gel electrophoresis. The G 1 peak of Hep3B cells was reduced. Chemically synthesized CAN 032 may provide an improved therapeutic advantage over traditional cantharidin.
ISSN: 1107-3756
EISSN: 1791-244X
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