Mar. Drugs 2016, 14(4), 69; https://doi.org/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
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-TextKeywords:
activating transcription factor 3; apoptosis; human colorectal cancer; phlorofucofuroeckol A; Eisenia bicyclis
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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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