This study was aimed to investigate the
biological behavior of annonaceous acetogenin mimic
AA005 in various kinds of
leukemia cells and further elaborated its possible mechanisms in
acute promyelocytic leukemia (APL) cell line NB4. The proliferative inhibition of
leukemia cells was measured by
CCK-8 method. Cell death was determined by
trypan blue. Cell morphological features of NB4 treated with
AA005 were examined by microscopy after Wright's staining. The form of cell death was measured by flow cytometry.
Proteins PARP-1 and
caspase-3 were detected by Western blot. Flow cytometry was used to detect the cell cycle arrest induced by
AA005 of low concentration. The results showed that
AA005 (> 200 nmol/L) significantly inhibited proliferation of all tested
leukemia cell lines in a concentration-dependent manner. The vast majority of cells went to die after
leukemia cell lines of NB4, U937 and K562 were treated with different concentration of
AA005 for 48 h. Typical morphologic changes significantly appeared in NB4 cells after
AA005 treatment.
AA005 almost simultaneously induced early apoptosis and late apoptosis. The little cleavage of PARP-1 and activation of
caspase-3 happened in AA005-induced cell death, and
caspase-3 inhibitor
Z-VAD-fmk could not block the cell death. The non-toxic concentrations of
AA005 (< 200 nmol/L) caused NB4 cells G(2)/M-phase arrest. It is concluded that annonaceous acetogenin mimic
AA005 induces significant proliferative inhibition of various
leukemia cell lines in a concentration-dependent manner, which may be associated with cell death and G(2)/M-phase arrest induced by
AA005.