Cryptotanshinone induces ROS-mediated apoptosis in human gastric cancer cells
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Chang Liu1,*, Hu-Nan Sun1,*, Ying-Hua Luo2,*, Xian-Ji Piao3,*, Dan-Dan Wu1, Ling-Qi Meng1, Yue Wang1, Yi Zhang1, Jia-Ru Wang1, Hao Wang1, Wan-Ting Xu1, Jin-Qian Li1, Yang Liu1, Yi-Qin Wu1, Ying-Hao Han1, Gui-Nan Shen1, Mei-Hua Jin1, Yan-Qing Zang4, Jing-Chun Li2, Nan-Zhu Fang5, Yu-Dong Cui1 and Cheng-Hao Jin1
1Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China
2College of Animal Science & Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
3Department of Gynaecology and Obstetrics, The Fifth Affiliated Hospital of Harbin Medical University, Daqing 163316, China
4College of Food Science & Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China
5Department of Animal Science, College of Agriculture, Yanbian University, Gongyuan-jie, Yanji 133002, China
*These authors have contributed equally to this study as first authors
Cheng-Hao Jin, email: email@example.com
Yu-Dong Cui, email: firstname.lastname@example.org
Keywords: cryptotanshinone; gastric cancer; apoptosis; cell cycle arrest; ROS
Received: July 14, 2017 Accepted: December 03, 2017 Published: December 15, 2017
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.
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