1-(3',4',5'-Trimethoxyphenyl)-3-(3'',4''-dimethoxy-2''-hydroxyphenyl)-propane with microtubule-depolymerizing ability induces G2/M phase arrest and apoptosis in HepG2 cells.
1-(3',4',5'-Trimethoxyphenyl)-3-(3'',4''-dimethoxy-2''-hydroxyphenyl)-propane (DP), a novel synthesized 1,3-diarylpropanes compound, showed growth inhibitory effect on human hepatoma HepG2 cells in a concentration-dependent manner. The growth inhibitory effect of DP on HepG2 cells was associated with microtubule depolymerization, G2/M phase arrest and apoptosis induction. The G2/M phase arrest induced by DP resulted from its microtubule-depolymerizing ability, and DP-treated HepG2 cells finally underwent caspase-dependent apoptosis. DP increased the levels of death receptor 4 (DR4), death receptor 5 (DR5) and pro-apoptotic protein Bax, but decreased the levels of anti-apoptotic protein Bcl-2. Meanwhile, the decrease in the mitochondrial membrane potential (MMP) and the release of cytochrome c from mitochondria were observed in DP-treated HepG2 cells. DP increased the levels of reactive oxygen species (ROS) in HepG2 cells, and antioxidant N-acetylcysteine (NAC) completely blocked DP-induced ROS accumulation and the disruption of the balance between Bax and Bcl-2 proteins, and effectively blocked the decreased MMP and apoptosis, but had no effect on the activation of caspase-8 and the up-regulations of DR4 and DR5 induced by DP. These results suggest that DP induces G2/M phase arrest through interruption of microtubule network followed by the death receptor- and ROS-mediated apoptosis in HepG2 cells.
Li
Shanshan
S
Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Tai
Wenjiao
W
Li
Yanchun
Y
Zhang
Liang
L
Zhang
Weige
W
Ma
Enlong
E
Li
Jianchun
J
D000840:Anisoles / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D008870:Microtubules / Q000187:drug effects*
C552420:1-(3',4',5'-trimethoxyphenyl)-3-(3'',4''-dimethoxy-2'-hydroxyphenyl)propane; D000840:Anisoles