Casticin Induces DNA Damage and Impairs DNA Repair in Human Bladder Cancer TSGH-8301 Cells

Anticancer Res. 2019 Apr;39(4):1839-1847. doi: 10.21873/anticanres.13291.

Abstract

Background/aim: Casticin shows anti-cancer effects in many types of cancer. However, there is no information regarding its role in DNA damage in human bladder cancer. The aim of this study was to investigate the effects of casticin on TSGH-8301 cells in vitro.

Materials and methods: Viability of cells was assayed by flow cytometry. DNA damage was assayed by DAPI staining, comet assay, and gel electrophoresis. Protein levels were examined by western blotting and confocal laser microscopy.

Results: Casticin decreased viability of cells and induced DNA damage. Furthermore, casticin decreased expression of p-ATM, p-ATR, MDC1 and MGMT levels after 48 h of treatment, however, it increased p-ATR and MGMT levels after 12 h. In contrast, casticin increased the levels of p-p53, p-H2A.X, and PARP after 48 h of treatment. As shown by confocal microscopy, casticin affected the translocation of DNA-PKcs and p-p53 to the nucleus of TSGH-8301 cells.

Conclusion: Casticin decreased viability of human bladder cancer cells through DNA damage.

Keywords: Casticin; DNA damage; DNA repair; TSGH-8301 human bladder cancer cells.

MeSH terms

  • Active Transport, Cell Nucleus
  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Damage*
  • DNA Modification Methylases / metabolism
  • DNA Repair / drug effects*
  • DNA Repair Enzymes / metabolism
  • DNA-Activated Protein Kinase / metabolism
  • Flavonoids / pharmacology*
  • Histones / metabolism
  • Humans
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Poly(ADP-ribose) Polymerases / metabolism
  • Trans-Activators / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / metabolism
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents, Phytogenic
  • Cell Cycle Proteins
  • Flavonoids
  • H2AX protein, human
  • Histones
  • MDC1 protein, human
  • Nuclear Proteins
  • TP53 protein, human
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • casticin
  • DNA Modification Methylases
  • MGMT protein, human
  • Poly(ADP-ribose) Polymerases
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • DNA Repair Enzymes