TY - JOUR
T1 - CYT-Rx20 inhibits ovarian cancer cells in vitro and in vivo through oxidative stress-induced DNA damage and cell apoptosis
AU - Wang, Yen Yun
AU - Chen, Yuk Kwan
AU - Hu, Stephen Chu Sung
AU - Hsu, Ya Ling
AU - Tsai, Chun Hao
AU - Chi, Tsung Chen
AU - Huang, Wan Ling
AU - Hsieh, Pei Wen
AU - Yuan, Shyng Shiou F.
N1 - Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Purpose: The β-nitrostyrene family has been previously reported to possess anticancer property. However, the biological effects of β-nitrostyrenes on ovarian cancer and the underlying mechanisms involved remain unclear. In the present study, we synthesized a β-nitrostyrene derivative, CYT-Rx20 3′-hydroxy-4′-methoxy-β-methyl-β-nitrostyrene), and investigated its anticancer effects and the putative pathways of action in ovarian cancer. Methods: The effects of CYT-Rx20 were analyzed using cell viability assay, reactive oxygen species (ROS) generation assay, FACS analysis, annexin V staining, immunostaining, comet assay, immunoblotting, soft agar assay, migration assay, nude mice xenograft study and immunohistochemistry. Results: CYT-Rx20 induced cytotoxicity in ovarian cancer cells by promoting cell apoptosis via ROS generation and DNA damage. CYT-Rx20-induced cell apoptosis, ROS generation and DNA damage were reversed by thiol antioxidants. In addition, CYT-Rx20 inhibited ovarian cancer cell migration by regulating the expression of epithelial to mesenchymal transition (EMT) markers. In nude mice, CYT-Rx20 inhibited ovarian tumor growth accompanied by increased expression of DNA damage marker γH2AX and decreased expression of EMT marker Vimentin. Conclusions: CYT-Rx20 inhibits ovarian cancer cells in vitro and in vivo, and has the potential to be further developed into an anti-ovarian cancer drug clinically.
AB - Purpose: The β-nitrostyrene family has been previously reported to possess anticancer property. However, the biological effects of β-nitrostyrenes on ovarian cancer and the underlying mechanisms involved remain unclear. In the present study, we synthesized a β-nitrostyrene derivative, CYT-Rx20 3′-hydroxy-4′-methoxy-β-methyl-β-nitrostyrene), and investigated its anticancer effects and the putative pathways of action in ovarian cancer. Methods: The effects of CYT-Rx20 were analyzed using cell viability assay, reactive oxygen species (ROS) generation assay, FACS analysis, annexin V staining, immunostaining, comet assay, immunoblotting, soft agar assay, migration assay, nude mice xenograft study and immunohistochemistry. Results: CYT-Rx20 induced cytotoxicity in ovarian cancer cells by promoting cell apoptosis via ROS generation and DNA damage. CYT-Rx20-induced cell apoptosis, ROS generation and DNA damage were reversed by thiol antioxidants. In addition, CYT-Rx20 inhibited ovarian cancer cell migration by regulating the expression of epithelial to mesenchymal transition (EMT) markers. In nude mice, CYT-Rx20 inhibited ovarian tumor growth accompanied by increased expression of DNA damage marker γH2AX and decreased expression of EMT marker Vimentin. Conclusions: CYT-Rx20 inhibits ovarian cancer cells in vitro and in vivo, and has the potential to be further developed into an anti-ovarian cancer drug clinically.
KW - Apoptosis
KW - Migration
KW - Ovarian cancer
KW - ROS
KW - β-Nitrostyrene
UR - http://www.scopus.com/inward/record.url?scp=85019183268&partnerID=8YFLogxK
U2 - 10.1007/s00280-017-3330-9
DO - 10.1007/s00280-017-3330-9
M3 - 文章
C2 - 28500555
AN - SCOPUS:85019183268
SN - 0344-5704
VL - 79
SP - 1129
EP - 1140
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 6
ER -
