Open AccessCryptotanshinone induces ROS-mediated apoptosis in human gastric cancer cells
Author(s) -
Chang Liu,
Haiyan Sun,
Yunping Luo,
XiangLan Piao,
Dandan Wu,
Meng Li,
Yue Wang,
Yi Zhang,
Jia-Ru Wang,
Hao Wang,
Wanting Xu,
Jin-Qian Li,
Liu Yang,
Yiqin Wu,
YingHao Han,
GuiNan Shen,
Meihua Jin,
Yanqing Zang,
Jingchun Li,
Fang Nan-zhu,
Yudong Cui,
ChengHao Jin
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.23267
Subject(s) - salvia miltiorrhiza , traditional medicine , medicine , china , apoptosis , traditional chinese medicine , cancer , cancer research , biology , pathology , alternative medicine , political science , biochemistry , law
Cryptotanshinone (CT), isolated from the plant Salvia miltiorrhiza Bunge , has been reported to have potential anticancer effects on human prostate and breast cancer cells. However, the mechanisms of action of CT on gastric cancer (GC) cells are not well understood. Here we investigated the antitumor effects of CT on GC cells and its possible molecular mechanism. We found CT suppressed viability of twelve GC cell lines in a dose-dependent manner. CT induced cell cycle arrest at the G2/M phase and mitochondrial apoptosis accompanying the accumulation of reactive oxygen species (ROS). Pretreatment with ROS inhibitor N-acetyl-L-cysteine (NAC) blocked CT-induced apoptosis. CT increased p-JNK and p-p38, and decreased p-ERK and p-STAT3 protein expression, these effects were prevented by NAC. Furthermore, a xenograft assay showed that CT significantly inhibited MKN-45 cell-induced tumor growth in vivo by increasing expression of pro-apoptotic proteins (p-JNK, p-38 and cleaved-caspase-3) and reducing expression of anti-apoptotic proteins (p-ERK and p-STAT3) without adverse effects on nude mice weight. In conclusion, CT induced apoptosis and cell cycle arrest in GC cells via ROS-mediated MAPK and AKT signaling pathways, and this CT may be a useful compound for the developing anticancer agents for GC.