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.