Radiosensitizer effect of β-apopicropodophyllin against colorectal cancer via induction of reactive oxygen species and apoptosis

Jin Hee Kwon, Na Gyeong Lee, A. Ram Kang, Jie Young Song, Sang Gu Hwang, Hong Duck Um, Joon Kim, Jong Kuk Park

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an anti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP exerted an anti-cancer effect against the CRC cell lines HCT116, DLD-1, SW480, and COLO320DM, with IC50 values of 7.88 nM, 8.22 nM, 9.84 nM, and 7.757 nM, respectively, for the induction of DNA damage. Clonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either treatment alone, suggesting that APP sensitized CRC cells to IR. Annexin V–propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in the in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

Original languageEnglish
Article number13514
JournalInternational journal of molecular sciences
Volume22
Issue number24
DOIs
Publication statusPublished - 2021 Dec 1

Keywords

  • Apoptosis
  • Col-orectal cancer
  • ROS
  • Radiosensitizer
  • Topoisomerase inhibitor
  • β-apopicropodophyllin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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