TY - JOUR
T1 - TQ inhibits hepatocellular carcinoma growth in vitro and in vivo via repression of Notch signaling
AU - Ke, Xiquan
AU - Zhao, Yan
AU - Lu, Xinlan
AU - Wang, Zhe
AU - Liu, Yuanyuan
AU - Ren, Mudan
AU - Lu, Guifang
AU - Zhang, Dan
AU - Sun, Zhenguo
AU - Xu, Zhipeng
AU - Song, Jee Hoon
AU - Cheng, Yulan
AU - Meltzer, Stephen J.
AU - He, Shuixiang
PY - 2015
Y1 - 2015
N2 - Thymoquinone (TQ) has been reported to possess anti-tumor activity in various types of cancer. However, its effects and molecular mechanism of action in hepatocellular carcinoma (HCC) are still not completely understood. We observed that TQ inhibited tumor cell growth in vitro, where treatment with TQ arrested the cell cycle in G1 by upregulating p21 and downregulating cyclinD1 and CDK2 expression; moreover, TQ induced apoptosis by decreasing expression of Bcl-2 and increasing expression of Bax. Simultaneously, TQ demonstrated a suppressive impact on the Notch pathway, where overexpression of NICD1 reversed the inhibitory effect of TQ on cell proliferation, thereby attenuating the repressive effects of TQ on the Notch pathway, cyclinD1, CDK2 and Bcl-2, and also diminishing upregulation of p21 and Bax. In a xenograft model, TQ inhibited HCC growth in nude mice; this inhibitory effect in vivo, as well as of HCC cell growth in vitro, was associated with a discernible decline in NICD1 and Bcl-2 levels and a dramatic rise in p21 expression. In conclusion, TQ inhibits HCC cell growth by inducing cell cycle arrest and apoptosis, achieving these effects by repression of the Notch signaling pathway, suggesting that TQ represents a potential preventive or therapeutic agent in HCC patients.
AB - Thymoquinone (TQ) has been reported to possess anti-tumor activity in various types of cancer. However, its effects and molecular mechanism of action in hepatocellular carcinoma (HCC) are still not completely understood. We observed that TQ inhibited tumor cell growth in vitro, where treatment with TQ arrested the cell cycle in G1 by upregulating p21 and downregulating cyclinD1 and CDK2 expression; moreover, TQ induced apoptosis by decreasing expression of Bcl-2 and increasing expression of Bax. Simultaneously, TQ demonstrated a suppressive impact on the Notch pathway, where overexpression of NICD1 reversed the inhibitory effect of TQ on cell proliferation, thereby attenuating the repressive effects of TQ on the Notch pathway, cyclinD1, CDK2 and Bcl-2, and also diminishing upregulation of p21 and Bax. In a xenograft model, TQ inhibited HCC growth in nude mice; this inhibitory effect in vivo, as well as of HCC cell growth in vitro, was associated with a discernible decline in NICD1 and Bcl-2 levels and a dramatic rise in p21 expression. In conclusion, TQ inhibits HCC cell growth by inducing cell cycle arrest and apoptosis, achieving these effects by repression of the Notch signaling pathway, suggesting that TQ represents a potential preventive or therapeutic agent in HCC patients.
KW - Apoptosis
KW - Cell cycle
KW - Hepatocellular carcinoma
KW - Notch
KW - Thymoquinone
UR - http://www.scopus.com/inward/record.url?scp=84946091500&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946091500&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.5362
DO - 10.18632/oncotarget.5362
M3 - Article
C2 - 26416455
AN - SCOPUS:84946091500
SN - 1949-2553
VL - 6
SP - 32610
EP - 32621
JO - Oncotarget
JF - Oncotarget
IS - 32
ER -