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Mar. Drugs 2016, 14(4), 69; doi:10.3390/md14040069

In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells

1
Department of Bioresource Sciences, Andong National University, Andong 36729, Korea
2
Chuncheon Bioindustry Foundation, Chuncheon 24234, Korea
3
Department of Herbal Medicine Resource, Kangwon National University, Dogye 25949, Korea
4
Gyeongbuk Institute for Marine Bioindustry, Uljin 36315, Korea
These authors equally contributed to this study.
*
Author to whom correspondence should be addressed.
Academic Editor: Keith B. Glaser
Received: 28 February 2016 / Revised: 18 March 2016 / Accepted: 24 March 2016 / Published: 29 March 2016
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Abstract

Phlorofucofuroeckol A (PFF-A), one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB), located between positions −147 and −85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK), glycogen synthase kinase (GSK) 3β, and IκB kinase (IKK)-α blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose) polymerase (PARP) by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells. View Full-Text
Keywords: activating transcription factor 3; apoptosis; human colorectal cancer; phlorofucofuroeckol A; Eisenia bicyclis activating transcription factor 3; apoptosis; human colorectal cancer; phlorofucofuroeckol A; Eisenia bicyclis
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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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MDPI and ACS Style

Eo, H.J.; Kwon, T.-H.; Park, G.H.; Song, H.M.; Lee, S.-J.; Park, N.-H.; Jeong, J.B. In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells. Mar. Drugs 2016, 14, 69.

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