Biomol Ther.  2017 May;25(3):337-343. 10.4062/biomolther.2016.114.

Kahweol from Coffee Induces Apoptosis by Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells

• Park GH
• Song HM
• Jeong JB

• KMID: 2378813
• DOI: http://doi.org/10.4062/biomolther.2016.114

Abstract

Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in human cancer cells. Although some molecular targets for kahweol-mediated apoptosis have been elucidated, the further mechanism for apoptotic effect of kahweol is not 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 kahweol stimulates ATF3 expression and apoptosis in human colorectal cancer cells. Kahweol increased apoptosis in human colorectal cancer cells. It also increased ATF3 expression through the transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by kahweol was CREB located between −147 to −85 of ATF3 promoter. ATF3 overexpression increased kahweol-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by kahweol. Inhibition of ERK1/2 and GSK3β blocked kahweol-mediated ATF3 expression. The results suggest that kahweol induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.

Keyword

Activating transcription factor 3; Apoptosis; Coffee; Human colorectal cancer; Kahweol

MeSH Terms

Activating Transcription Factor 3*
Apoptosis*
Coffee*
Colorectal Neoplasms*
Humans*
Transcriptional Activation
Activating Transcription Factor 3
Coffee