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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 (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Lim, Man Sup (Department of Pharmacology, Kangwon National University School of Medicine) ;
  • Lee, Jae Won (Department of Pharmacology, Kangwon National University School of Medicine) ;
  • Chun, Wanjoo (Department of Pharmacology, Kangwon National University School of Medicine) ;
  • Lee, Sang Hyuk (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Nam, Yang Hoon (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Park, Jin Myung (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Choi, Dae Hee (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Kang, Chang Don (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Lee, Sung Joon (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Park, Sung Chul (Department of Internal Medicine, Kangwon National University School of Medicine)
  • Received : 2014.12.01
  • Accepted : 2014.12.23
  • Published : 2015.03.01

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.

Keywords

References

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