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Int. J. Mol. Sci. 2016, 17(4), 558; doi:10.3390/ijms17040558

Induction of ROS Overload by Alantolactone Prompts Oxidative DNA Damage and Apoptosis in Colorectal Cancer Cells

1
Department of Radiotherapy, the Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China
2
School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun 130012, China
3
Department of Nephrology, the Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China
4
Department of Thoracic Oncology, Jilin Provincial Cancer Hospital, 1018 Huguang Street, Changchun 130012, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Anthony Lemarié
Received: 23 February 2016 / Revised: 17 March 2016 / Accepted: 8 April 2016 / Published: 14 April 2016
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
View Full-Text   |   Download PDF [1922 KB, uploaded 14 April 2016]   |  

Abstract

Cancer cells typically display higher than normal levels of reactive oxygen species (ROS), which may promote cancer development and progression but may also render the cancer cells more vulnerable to further ROS insult. Indeed, many of the current anticancer therapeutics kill cancer cells via induction of oxidative stress, though they target both cancer and normal cells. Recently, alantolactone (ATL), a natural sesquiterpene lactone, has been shown to induce apoptosis by increasing ROS levels specifically in cancer cells; however, the molecular mechanisms linking ROS overproduction to apoptosis remain unclear. Here we show that the ATL-induced ROS overload in human SW480 and SW1116 colorectal cancer cells was followed by a prominent accumulation of cellular oxidized guanine (8-oxoG) and immediate increase in the number of DNA strand breaks, indicating that increased ROS resulted in extensive oxidative DNA damage. Consequently, the G1/S-CDK suppresser CDKN1B (p21) and pro-apoptotic proteins Bax and activated caspase-3 were upregulated, while anti-apoptotic Bcl-2 was downregulated, which were followed by cell cycle arrest at G1 and marked apoptosis in ATL-treated cancer but not non-cancer cells. These results suggest that the ATL-induced ROS overload triggers cell death through induction of massive oxidative DNA damage and subsequent activation of the intrinsic apoptosis pathway. View Full-Text
Keywords: alantolactone; DNA damage; 8-oxoG; apoptosis; cell cycle arrest; colorectal cancer alantolactone; DNA damage; 8-oxoG; apoptosis; cell cycle arrest; colorectal cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ding, Y.; Wang, H.; Niu, J.; Luo, M.; Gou, Y.; Miao, L.; Zou, Z.; Cheng, Y. Induction of ROS Overload by Alantolactone Prompts Oxidative DNA Damage and Apoptosis in Colorectal Cancer Cells. Int. J. Mol. Sci. 2016, 17, 558.

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