Article Text

Download PDFPDF
CYT-Rx20 Inhibits Cervical Cancer Cell Growth and Migration Through Oxidative Stress-Induced DNA Damage, Cell Apoptosis, and Epithelial-to-Mesenchymal Transition Inhibition
  1. Yen-Yun Wang, PhD*,
  2. Pei-Wen Hsieh, PhD,,
  3. Yuk-Kwan Chen, DDS, MS§,,
  4. Stephen Chu-Sung Hu, MD, PhD#,**,
  5. Ya-Ling Hsu, MS*,
  6. Chun-Hao Tsai, MS, and
  7. Shyng-Shiou F. Yuan, MD, PhD*,††,‡‡,§§
  1. * Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung;
  2. Graduate Institute of Natural Products, School of Traditional Chinese Medicine, and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University;
  3. Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan;
  4. § Division of Oral Pathology and Maxillofacial Radiology, Kaohsiung Medical University Hospital;
  5. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University;
  6. Oral and Maxillofacial Imaging Center, College of Dental Medicine, Kaohsiung Medical University;
  7. # Department of Dermatology, College of Medicine, Kaohsiung Medical University;
  8. ** Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University;
  9. †† Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University;
  10. ‡‡ Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University; and
  11. §§ Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
  1. Address correspondence and reprint requests to Shyng-Shiou F. Yuan, MD, PhD, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No 100, Tzyou 1st Road, Kaohsiung 807, Taiwan. E-mail: yuanssf{at}kmu.edu.tw.

Abstract

Objective The β-nitrostyrene family has been reported to possess anticancer properties. However, the anticancer activity of β-nitrostyrenes on cervical cancer cells and the underlying mechanisms involved remain unexplored. In this study, a β-nitrostyrene derivative CYT-Rx20 (3′-hydroxy-4′-methoxy-β-methyl-β-nitrostyrene) was synthesized, and its anticancer activity on cervical cancer cells and the mechanisms involved were investigated.

Methods The effect of CYT-Rx20 on human cervical cancer cell growth was evaluated using cell viability assay. Reactive oxygen species (ROS) generation and annexin V staining were detected by flow cytometry. The protein expression levels of cleaved caspase-3, cleaved caspase-9, cleaved poly (ADPribose) polymerase, γH2AX, β-catenin, Vimentin, and Twist were measured by Western blotting. DNA double-strand breaks were determined by γ-H2AX foci formation and neutral comet assay. Migration assay was used to determine cancer cell migration. Nude mice xenograft was used to investigate the antitumor effects of CYT-Rx20 in vivo.

Results CYT-Rx20 induced cytotoxicity in cervical 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 cervical cancer cell migration by regulating the expression of epithelial-to-mesenchymal transition markers. In nude mice, CYT-Rx20 inhibited cervical tumor growth accompanied by increased expression of DNA damage marker γH2AX and decreased expression of mesenchymal markers β-catenin and Twist.

Conclusions CYT-Rx20 inhibits cervical cancer cells in vitro and in vivo and has the potential to be further developed into an anti-cervical cancer drug clinically.

  • β-Nitrostyrene
  • ROS
  • DNA damage
  • Apoptosis
  • Migration
  • Cervical cancer

Statistics from Altmetric.com

Footnotes

  • The authors declare that there are no conflicts of interest.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.