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

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 ana...

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Autores principales: KWAK, SEO-YOUNG, JEONG, YOUN KYOUNG, KIM, BU-YEON, LEE, JI YOUNG, AHN, HYUN-JOO, JEONG, JAE-HOON, KIM, MI-SOOK, KIM, JOON, HAN, YOUNG-HOON
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049772/
https://www.ncbi.nlm.nih.gov/pubmed/24932238
http://dx.doi.org/10.3892/ol.2014.2018
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author KWAK, SEO-YOUNG
JEONG, YOUN KYOUNG
KIM, BU-YEON
LEE, JI YOUNG
AHN, HYUN-JOO
JEONG, JAE-HOON
KIM, MI-SOOK
KIM, JOON
HAN, YOUNG-HOON
author_facet KWAK, SEO-YOUNG
JEONG, YOUN KYOUNG
KIM, BU-YEON
LEE, JI YOUNG
AHN, HYUN-JOO
JEONG, JAE-HOON
KIM, MI-SOOK
KIM, JOON
HAN, YOUNG-HOON
author_sort KWAK, SEO-YOUNG
collection PubMed
description 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.
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spelling pubmed-40497722014-06-13 β,β-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species KWAK, SEO-YOUNG JEONG, YOUN KYOUNG KIM, BU-YEON LEE, JI YOUNG AHN, HYUN-JOO JEONG, JAE-HOON KIM, MI-SOOK KIM, JOON HAN, YOUNG-HOON Oncol Lett Articles 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. D.A. Spandidos 2014-06 2014-03-31 /pmc/articles/PMC4049772/ /pubmed/24932238 http://dx.doi.org/10.3892/ol.2014.2018 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
KWAK, SEO-YOUNG
JEONG, YOUN KYOUNG
KIM, BU-YEON
LEE, JI YOUNG
AHN, HYUN-JOO
JEONG, JAE-HOON
KIM, MI-SOOK
KIM, JOON
HAN, YOUNG-HOON
β,β-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species
title β,β-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species
title_full β,β-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species
title_fullStr β,β-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species
title_full_unstemmed β,β-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species
title_short β,β-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species
title_sort β,β-dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049772/
https://www.ncbi.nlm.nih.gov/pubmed/24932238
http://dx.doi.org/10.3892/ol.2014.2018
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