We recently established that
LL-202, a newly synthesized
flavonoid, exhibited obvious anticancer effects against human breast cells in vivo and in vitro. The underlying mechanism of its anticancer activity remains to be elucidated. In this study, we demonstrated that
LL-202 inhibited the growth and proliferation of human
breast cancer MCF-7 cells in a concentration and time-dependent manner. We reported that
LL-202 induced both mitochondrial- and
death-receptor-mediated apoptosis, which were characterized by the dissipation of mitochondrial membrane potential (ΔΨm),
cytochrome c (Cyt c) release from mitochondria to cytosol, the activation of several
caspases and induction of
poly (ADP-ribose) polymerase (PARP) and Bid cleavage.
N-acetylcysteine (NAC), a general ROS scavenger, partly blocked the LL-202-induced ROS levels and apoptosis. In addition,
LL-202 induced arrest in cell cycle progression at G2/M phase in MCF-7 cells. After the treatment with
LL-202, the expression of cell cycle-related
proteins, such as
cyclin B1,
cyclin A, and p-CDK1 (Thr161) were down-regulated, whereas the expression of p21(WAF1/Cip1) and p-CDK1 (Thr14/Tyr15) were up-regulated. Finally, in vivo studies,
LL-202 significantly suppressed the growth of MCF-7
breast cancer xenograft
tumors in a dose-dependent manner with low systemic toxicity. In conclusion, the results showed that
LL-202 had significant anticancer effects against human breast cells via the induction of apoptosis and G2/M phase arrest and it may be a novel
anticancer agent for treatment of
breast cancer.