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

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

  • Published online on: December 1, 2006     https://doi.org/10.3892/ijmm.18.6.1217
  • Pages: 1217-1221
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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.

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December 2006
Volume 18 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kok SH, Chui CH, Lam WS, Chen J, Lau FY, Wong RS, Cheng GY, Tang WK, Teo IT, Cheung F, Cheung F, et al: Apoptogenic activity of a synthetic cantharimide in leukaemia: Implication on its structural activity relationship. Int J Mol Med 18: 1217-1221, 2006.
APA
Kok, S.H., Chui, C.H., Lam, W.S., Chen, J., Lau, F.Y., Wong, R.S. ... Tang, J.C. (2006). Apoptogenic activity of a synthetic cantharimide in leukaemia: Implication on its structural activity relationship. International Journal of Molecular Medicine, 18, 1217-1221. https://doi.org/10.3892/ijmm.18.6.1217
MLA
Kok, S. H., Chui, C. H., Lam, W. S., Chen, J., Lau, F. Y., Wong, R. S., Cheng, G. Y., Tang, W. K., Teo, I. T., Cheung, F., Cheng, C. H., Chan, A. S., Tang, J. C."Apoptogenic activity of a synthetic cantharimide in leukaemia: Implication on its structural activity relationship". International Journal of Molecular Medicine 18.6 (2006): 1217-1221.
Chicago
Kok, S. H., Chui, C. H., Lam, W. S., Chen, J., Lau, F. Y., Wong, R. S., Cheng, G. Y., Tang, W. K., Teo, I. T., Cheung, F., Cheng, C. H., Chan, A. S., Tang, J. C."Apoptogenic activity of a synthetic cantharimide in leukaemia: Implication on its structural activity relationship". International Journal of Molecular Medicine 18, no. 6 (2006): 1217-1221. https://doi.org/10.3892/ijmm.18.6.1217