Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation

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Title
Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation
Author(s)
Osong Kwon; Nak Kyun Soung; N R Thimmegowda; S J Jeong; JaeHyuik Jang; D O Moon; J K Chung; K S Lee; Y T Kwon; R L Erikson; Jong Seog AhnBo Yeon Kim
Bibliographic Citation
Cellular Signalling, vol. 24, no. 4, pp. 943-950
Publication Year
2012
Abstract
Patulin is a fungal mycotoxin of Aspergilus and Penicillium that is commonly found in rotting fruits and exerts its potential toxic effect mainly by reactive oxygen species (ROS) generation. However, the effect of patulin on cancer cells as well as its intracellular mechanism has been controversial and not clearly defined yet. In this study, patulin was found to induce G1/S accumulation and cell growth arrest accompanied by caspase-3 activation, PARP cleavage and ATF3 expression in human colon cancer cell line HCT116. Ser/Thr phosphorylation of a transcription factor, EGR-1, was increased while its expression did not change upon patulin treatment to the cells. Knockdown of ATF3 and EGR-1 using their respective siRNAs showed EGR-1 dependent ATF3 expression. Moreover, treatment of the cells with antioxidants N-acetylcysteine (NAC) and glutathione (GSH) revealed that patulin induced ATF3 expression and apoptosis were dependent on ROS generation. ATF3 expression was also increased by patulin in other colorectal cancer cell types, Caco2 and SW620. Collectively, our data present a new anti-cancer molecular mechanism of patulin, suggesting EGR-1 and ATF3 as critical targets for the development of anti-cancer chemotherapeutics. In this regard, patulin could be a candidate for the treatment of colorectal cancers.
Keyword
ATF3EGR-1PatulinROS
ISSN
0898-6568
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.cellsig.2011.12.017
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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