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 G1 peak of Hep3B cells was reduced. Chemically synthesized
CAN 032 may provide an improved therapeutic advantage over traditional
cantharidin.