Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/8339
Title: Mechanistic insight into a novel synthetic cantharidin analogue in a leukaemia model
Authors: Kok, SHL
Chui, CH
Lam, WS
Chen, J
Lau, FY
Wong, RSM
Cheng, GYM
Tang, WK
Cheng, CH
Tang, JCO 
Chan, ASC
Keywords: Cantharidin
Caspase
Leukaemia
Issue Date: 2006
Publisher: Spandidos Publications
Source: International journal of molecular medicine, 2006, v. 18, no. 2, p. 375-379 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 especially on hepatoma and leukaemia. Previously, we demonstrated that the novel synthetic cantharidin analogue CAN 032 possessed apoptotic activity on two human hepatoma cell lines Hep3B hepatocellular carcinoma and SK-Hep-1 liver adenocarcinoma. However, its underlying mechanistic action on cancer cells remained unclear. Herein, we furthered our work by making use of KG1a acute myelogenous leukaemia (AML) and K562 chronic myelogenous leukaemia (CML) as experimental models. As anticipated, both leukaemia cell lines were sensitive to the cytotoxic action of CAN 032. The activity of CAN 032 was both dose- and time-course-dependent. CAN 032 readily inhibited the colony formation potential of both leukaemia cell lines. KG1a AML treated with CAN032 decreased G1 phase cell population, mitochondrial membrane potential collapse, caspase 3 activation and hence DNA fragmentation. Pre-incubation of leukaemia cells with the general caspase inhibitor Z-VAD-FMK could partially reversed the apoptotic action of CAN 032. This result suggested that the caspase-dependent pathway is necessary for the apoptotic action of CAN 032. CAN 032 provides a new direction for novel drug discovery in experimental cancer therapy.
URI: http://hdl.handle.net/10397/8339
ISSN: 1107-3756
EISSN: 1791-244X
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