title: β,β-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species.
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 examinedin vivousing the xenograft mouse model. Consistent with thein vitroresults, 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.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 139-706, Republic of Korea ; Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Seo-Young
authors.initials: SY
authors.lastname: Kwak
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Jeong
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Bu-Yeon
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Ahn
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul 139-706, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Han
keywords: apoptosis; radiosensitizer; reactive oxygen species; shikonin; β,β-dimethylacrylshikonin