The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression
Although coffee is known to have antioxidant, anti-inflammatory, and antitumor properties, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significant...
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The Korean Society of Applied Pharmacology
2015
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pubmed-43543132015-03-12 The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression Choi, Dong Wook Lim, Man Sup Lee, Jae Won Chun, Wanjoo Lee, Sang Hyuk Nam, Yang Hoon Park, Jin Myung Choi, Dae Hee Kang, Chang Don Lee, Sung Joon Park, Sung Chul Original Article Although coffee is known to have antioxidant, anti-inflammatory, and antitumor properties, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significantly elevated in many tumors and is accompanied by increased cell proliferation, metastasis and poor response to chemotherapy. In this study, we investigated the cytotoxicity of four bioactive compounds in coffee, namely, caffeine, caffeic acid, chlorogenic acid, and kahweol, in HT-29 human colon adenocarcinoma cells. Only kahweol showed significant cytotoxicity. Specifically, kahweol increased the expression of caspase-3, a pro-apoptotic factor, and decreased the expression of anti-apoptotic factors, such as Bcl-2 and phosphorylated Akt. In addition, kahweol significantly attenuated the expression of HSP70. Inhibition of HSP70 activity with triptolide increased kahweol-induced cytotoxicity. In contrast, overexpression of HSP70 significantly reduced kahweol-induced cell death. Taken together, these results demonstrate that kahweol inhibits colorectal tumor cell growth by promoting apoptosis and suppressing HSP70 expression. The Korean Society of Applied Pharmacology 2015-03 2015-03-01 /pmc/articles/PMC4354313/ /pubmed/25767680 http://dx.doi.org/10.4062/biomolther.2014.133 Text en Copyright © 2015 The Korean Society of Applied Pharmacology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
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Open Access Journal |
institution_category |
Foreign Institution |
institution |
US National Center for Biotechnology Information |
building |
NCBI PubMed |
collection |
Online Access |
language |
English |
format |
Online |
author |
Choi, Dong Wook Lim, Man Sup Lee, Jae Won Chun, Wanjoo Lee, Sang Hyuk Nam, Yang Hoon Park, Jin Myung Choi, Dae Hee Kang, Chang Don Lee, Sung Joon Park, Sung Chul |
spellingShingle |
Choi, Dong Wook Lim, Man Sup Lee, Jae Won Chun, Wanjoo Lee, Sang Hyuk Nam, Yang Hoon Park, Jin Myung Choi, Dae Hee Kang, Chang Don Lee, Sung Joon Park, Sung Chul The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression |
author_facet |
Choi, Dong Wook Lim, Man Sup Lee, Jae Won Chun, Wanjoo Lee, Sang Hyuk Nam, Yang Hoon Park, Jin Myung Choi, Dae Hee Kang, Chang Don Lee, Sung Joon Park, Sung Chul |
author_sort |
Choi, Dong Wook |
title |
The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression |
title_short |
The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression |
title_full |
The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression |
title_fullStr |
The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression |
title_full_unstemmed |
The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression |
title_sort |
cytotoxicity of kahweol in ht-29 human colorectal cancer cells is mediated by apoptosis and suppression of heat shock protein 70 expression |
description |
Although coffee is known to have antioxidant, anti-inflammatory, and antitumor properties, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significantly elevated in many tumors and is accompanied by increased cell proliferation, metastasis and poor response to chemotherapy. In this study, we investigated the cytotoxicity of four bioactive compounds in coffee, namely, caffeine, caffeic acid, chlorogenic acid, and kahweol, in HT-29 human colon adenocarcinoma cells. Only kahweol showed significant cytotoxicity. Specifically, kahweol increased the expression of caspase-3, a pro-apoptotic factor, and decreased the expression of anti-apoptotic factors, such as Bcl-2 and phosphorylated Akt. In addition, kahweol significantly attenuated the expression of HSP70. Inhibition of HSP70 activity with triptolide increased kahweol-induced cytotoxicity. In contrast, overexpression of HSP70 significantly reduced kahweol-induced cell death. Taken together, these results demonstrate that kahweol inhibits colorectal tumor cell growth by promoting apoptosis and suppressing HSP70 expression. |
publisher |
The Korean Society of Applied Pharmacology |
publishDate |
2015 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354313/ |
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1613196896182992896 |