title: The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression.
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.
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea ; Department of Surgery, Hallym University Sacred Heart Hospital, Anyang 431-796, Republic of Korea.
authors.forename: Man Sup
authors.initials: MS
authors.lastname: Lim
authors.affiliation: Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Yang Hoon
authors.initials: YH
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Jin Myung
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Dae Hee
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Chang Don
authors.initials: CD
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 200-701, Republic of Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Park
keywords: Apoptosis; Colorectal cancer; Heat shock protein 70; Kahweol