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Arch Biochem Biophys. 2014 Dec 15;564:203-10. doi: 10.1016/j.abb.2014.10.005. Epub 2014 Oct 22.

The contribution of activating transcription factor 3 to apoptosis of human colorectal cancer cells by protocatechualdehyde, a naturally occurring phenolic compound.

Author information

1
Gyeongbuk Institute for Bio-industry, Andong 760380, Republic of Korea.
2
Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
3
Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea; Institute of Agricultural Science and Technology, Andong National University, Andong 760749, Republic of Korea. Electronic address: jjb0403@anu.ac.kr.

Abstract

Protocatechualdehyde (PCA) is one of the important compounds found in barley, green cavendish bananas and grapevine leaves. PCA shows anti-cancer activities in breast, leukemia and colorectal cancer cells. Previous study reported that PCA exerts anti-cancer activity through down-regulating cyclin D1 and HDAC2 in human colorectal cancer cells. However, the underlying mechanisms for the expression of activating transcription factor 3 (ATF3) by PCA has not been studied. Thus, we performed in vitro study to investigate if treatment of PCA affects ATF3 expression and ATF3-mediated apoptosis in human colorectal cancer cells. PCA decreased cell viability in a dose-dependent manner in HCT116 and SW480 cells. In addition, PCA reduced cell viability in MCF-7, MDA-MB-231 and HepG-2 cells. Exposure of PCA activated the levels of ATF3 protein and mRNA in HCT116 and SW480 cells. Inhibition of ERK1/2/ by PD98059 and p38 by SB203580 inhibited PCA-induced ATF3 expression and transcriptional activation. ATF3-knockdown inhibited PCA-induced apoptosis and cell viability. In addition, ATF3 overexpression enhanced PCA-mediated cleavage of PARP. These findings suggest that inhibition of cell viability and apoptosis by PCA may be result of ATF3 expression through ERK1/2 and p38-mediated transcriptional activation.

KEYWORDS:

Activating transcription factor 3; Apoptosis; Chemoprevention; Colorectal cancer; Protocatechualdehyde

PMID:
25447816
DOI:
10.1016/j.abb.2014.10.005
[Indexed for MEDLINE]

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