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- Title
CYT-Rx20 inhibits ovarian cancer cells in vitro and in vivo through oxidative stress-induced DNA damage and cell apoptosis.
- Authors
Wang, Yen-Yun; Chen, Yuk-Kwan; Hu, Stephen; Hsu, Ya-Ling; Tsai, Chun-Hao; Chi, Tsung-Chen; Huang, Wan-Ling; Hsieh, Pei-Wen; Yuan, Shyng-Shiou; Hu, Stephen Chu-Sung; Yuan, Shyng-Shiou F
- Abstract
<bold>Purpose: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
STYRENE derivatives; CANCER cell migration; OVARIAN cancer; OXIDATIVE stress; CANCER cell growth; DNA damage; APOPTOSIS; PREVENTION; REACTIVE oxygen species; AGAR; ANIMAL experimentation; ANTINEOPLASTIC agents; CELL lines; CELL physiology; CELL motility; CYTOSKELETAL proteins; DNA; ELECTROPHORESIS; MICE; OVARIAN tumors; PROTEINS; BENZYLIDENE compounds; PHARMACODYNAMICS
- Publication
Cancer Chemotherapy & Pharmacology, 2017, Vol 79, Issue 6, p1129
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-017-3330-9