β,β-dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species

Seo Young Kwak, Youn Kyoung Jeong, Bu Yeon Kim, Ji Young Lee, Hyun Joo Ahn, Jae Hoon Jeong, Mi Sook Kim, Joon Kim, Young Hoon Han

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Shikonin, a naphthoquinone derivative, has been shown to possess antitumor activity. In the present study, the effects of shikonin and its analog, β,β-dimethylacrylshikonin, were investigated as radiosensitizers on the human colon cancer cell line, HCT-116. Shikonin and, to a greater extent, its analog-induced apoptosis of HCT-116 cells further synergistically potentiated the induction of apoptosis when combined with ionizing radiation (IR) treatment. Shikonins also stimulated an increase in reactive oxygen species (ROS) production and IR-induced DNA damage. Pre-treatment with the ROS scavenger, N-acetylcysteine, suppressed the enhancement of IR-induced DNA damage and apoptosis stimulated by shikonins, indicating that shikonins exert their radiosensitizing effects through ROS upregulation. The radiosensitizing effect of shikonins was also examined in vivo using the xenograft mouse model. Consistent with the in vitro results, injection of β,β-dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. Taken together, the results show that β,β-dimethylacrylshikonin is a promising agent for developing an improved strategy for radiotherapy against tumors.

Original languageEnglish
Pages (from-to)1812-1818
Number of pages7
JournalOncology Letters
Volume7
Issue number6
DOIs
Publication statusPublished - 2014 Jun

Keywords

  • Apoptosis
  • Radiosensitizer
  • Reactive oxygen species
  • Shikonin
  • β,β-dimethylacrylshikonin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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