Inhibition of HL-60 cell growth via cell cycle arrest and apoptosis induction by a cycloartane–labdane heterodimer from Pseudolarix amabilis

Pseudolaridimer C (1), a rarely encountered cycloartane-labdane Diels-Alder adduct was isolated from the cones of Pseudolarix amabilis. The structure and absolute configuration of 1 were established by comprehensive NMR and CD spectral analysis. The WST-8 assay indicated that 1 time and dose dependently inhibited the proliferation of human leukemia cells HL-60 at 1-10 mu M. DAPI and Annexin V-FITC/PI double staining method, and DNA ladder experiments all proved that 1 had significant dose-dependent effects on HL-60 cell apoptosis. A further mechanism study indicated that the apoptosis was associated with the cell cycle arrest during the G2/M phase, and the activation of caspase-9, -3, -7, and poly-(ADP-ribose)-polymerase (PARP).