Curcumin Induces Radiosensitivity of in Vitro and in Vivo Cancer Models by Modulating pre-mRNA Processing Factor 4 (Prp4)

Chem Biol Interact. 2013 Nov 25;206(2):394-402. doi: 10.1016/j.cbi.2013.10.007. Epub 2013 Oct 19.

Abstract

Radiation therapy plays a central role in adjuvant strategies for the treatment of both pre- and post-operative human cancers. However, radiation therapy has low efficacy against cancer cells displaying radio-resistant phenotypes. Ionizing radiation has been shown to enhance ROS generation, which mediates apoptotic cell death. Further, concomitant use of sensitizers with radiation improves the efficiency of radiotherapy against a variety of human cancers. Here, the radio-sensitizing effect of curcumin (a derivative of turmeric) was investigated against growth of HCT-15 cells and tumor induction in C57BL/6J mice. Ionizing radiation induced apoptosis through ROS generation and down-regulation of Prp4K, which was further potentiated by curcumin treatment. Flow cytometry revealed a dose-dependent response for radiation-induced cell death, which was remarkably reversed by transfection of cells with Prp4K clone. Over-expression of Prp4K resulted in a significant decrease in ROS production possibly through activation of an anti-oxidant enzyme system. To elucidate an integrated mechanism, Prp4K knockdown by siRNA ultimately restored radiation-induced ROS generation. Furthermore, B16F10 xenografts in C57BL/6J mice were established in order to investigate the radio-sensitizing effect of curcumin in vivo. Curcumin significantly enhanced the efficacy of radiation therapy and reduced tumor growth as compared to control or radiation alone. Collectively, these results suggest a novel mechanism for curcumin-mediated radio-sensitization of cancer based on ROS generation and down-regulation of Prp4K.

Keywords: Apoptosis; Cancer; Curcumin; ROS; Radio-sensitizer; Radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Disease Models, Animal
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • RNA Splicing Factors
  • RNA, Small Interfering / metabolism
  • Radiation, Ionizing
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Ribonucleoprotein, U4-U6 Small Nuclear / antagonists & inhibitors
  • Ribonucleoprotein, U4-U6 Small Nuclear / genetics
  • Ribonucleoprotein, U4-U6 Small Nuclear / metabolism*
  • Transplantation, Homologous

Substances

  • RNA Splicing Factors
  • RNA, Small Interfering
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • Protein-Serine-Threonine Kinases
  • Prpf4b protein, mouse
  • Curcumin