Induction of apoptosis on carcinoma cells by two synthetic cantharidin analogues

Stanton Hon Lung Kok, Chung Hin Chui, Wing Sze Lam, Jien Chen, Cheuk On Tang, Fung Yi Lau, Gregory Yin Ming Cheng, Raymond Siu Ming Wong, Albert Sun Chi Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

29 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. 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.
Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalInternational Journal of Molecular Medicine
Volume17
Issue number1
Publication statusPublished - 1 Jan 2006

Keywords

  • Apoptosis
  • Cantharidin
  • Carcinoma

ASJC Scopus subject areas

  • Genetics

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