Apoptogenic activity of a synthetic cantharimide in leukaemia: Implication on its structural activity relationship

Stanton Hon Lung Kok, Chung Hin Chui, Wing Sze Lam, Jien Chen, Fung Yi Lau, Raymond Siu Ming Wong, Gregory Yin Ming Cheng, Wing Ka Tang, Ivy Tuang Ngo Teo, Filly Cheung, Chor Hing Cheng, Albert Sun Chi Chan, Cheuk On Tang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

18 Citations (Scopus)

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. A synthetic analogue of cantharidin (CAN 037) has been shown to have cytotoxic effect on the SK-Hep 1 hepatoma cell line but its underlying working principle remains undefined. Here we further report the action of CAN 037 on an acute myelogenous leukaemia (AML) cell line, KG1a. [3-(4,5-dimethylthiazol-2-yl) -5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] (MTS) assay was used to demonstrate the cytotoxicity of CAN 037 on KG1a cells. Morphological changes of CAN 037-treated leukaemia cells were recorded under an inverted microscope. Possible activation of caspase 3, 8 and 9 from KG1a cells was also investigated. KG1a AML cells were sensitive to CAN 037. Morphological changes including cell shrinkage and loss of colony formation ability were observed. Caspase 3, 8 and 9 activity was elevated, whereas pre-incubating the KG1a cells with the generic caspase inhibitor z-VAD-fmk could only partially reverse the CAN 037-induced cell death. In addition to the SK-Hep-1 hepatoma cell line, CAN 037 is also effective in inducing the death of KG1a AML cells in vitro. Apoptosis is involved in the action of CAN 037 including the activation of the caspase family. Caspase-dependent cell death pathway may be necessary but not essential in CAN 037-induced apoptosis of KG1a cells. Further consideration of the structural activity relationship of CAN 037 may provide opportunities to improve its therapeutic value.
Original languageEnglish
Pages (from-to)1217-1221
Number of pages5
JournalInternational Journal of Molecular Medicine
Volume18
Issue number6
Publication statusPublished - 1 Dec 2006

Keywords

  • Cantharimide
  • Leukaemia
  • Structural activity relationship

ASJC Scopus subject areas

  • Genetics

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