title: Curcumin induces radiosensitivity of in vitro and in vivo cancer models by modulating pre-mRNA processing factor 4 (Prp4).
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.
authors.affiliation: School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Adeeb
authors.initials: A
authors.lastname: Shehzad
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D000072260:RNA Splicing Factors; D034741:RNA, Small Interfering / Q000378:metabolism; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D000072260:RNA Splicing Factors; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D017346:Protein Serine-Threonine Kinases; C489983:Prpf4b protein, mouse; D003474:Curcumin
keywords: Apoptosis; Cancer; Curcumin; ROS; Radio-sensitizer; Radiotherapy