Induction of G1 arrest and apoptosis mediated by a novel nucleoside analog, LJ-331 in human leukemia HL-60 cells

In a continuous effort to develop novel anticancer agents we newly synthesized and evaluated the antitumor activity of nucleoside analogues. One analogue, 4 - ［2-Chlor-6- (3-iodo- benzy lamino) -purin -9-yl］- 2,3-dihydroxy-cyclopentanecarbo xylic acid methylamide (LJ-331), has been shown to exert a potent inhibition of human cancer cell growth in vitro including human lung (A549), stomach (SNU-638) and leukemia (HL-60) cancer cells. Following mechanism of action study revealed that LJ - 331induces cell cycle arrest at the G1 phase in HL-60 cells and evokes apoptotic phenomena such as an increase in DNA ladder intensity and chromatin condensation by a dose- and time-dependent manner. LJ-331 also activated the caspase-3 activity in HL-60. This result suggests that the growth inhibition of human cancer cells by LJ-331 might be related to the cell cycle arrest and induction of apoptosis.