Biomol Ther.  2015 Mar;23(2):128-133. 10.4062/biomolther.2014.133.

The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression

Affiliations
  • 1Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea. schlp@hanmail.net
  • 2Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
  • 3Department of Surgery, Hallym University Sacred Heart Hospital, Anyang 431-796, Republic of Korea.

Abstract

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.

Keyword

Kahweol; Apoptosis; Heat shock protein 70; Colorectal cancer

MeSH Terms

Adenocarcinoma
Apoptosis*
Caffeine
Caspase 3
Cell Death
Cell Proliferation
Chlorogenic Acid
Coffee
Colon
Colorectal Neoplasms*
Drug Therapy
Heat-Shock Proteins
HSP70 Heat-Shock Proteins*
Humans
Molecular Chaperones
Neoplasm Metastasis
Caffeine
Caspase 3
Chlorogenic Acid
Coffee
HSP70 Heat-Shock Proteins
Heat-Shock Proteins
Molecular Chaperones
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