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

Biomolecules & Therapeutics
Dong Wook ChoiSung Chul Park

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.

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Citations

Feb 24, 2016·Biomolecules & Therapeutics·Jingyun YaoRenxiang Tan
Jul 18, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Gwang Hun ParkJin Boo Jeong
May 17, 2017·Natural Product Research·Jin Soo KimJu-Ock Nam
Oct 3, 2018·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Atena SoleimaniSeyed Mahdi Hassanian
Aug 24, 2019·IUBMB Life·Reyhaneh Moradi-MarjanehMahdi Moradi Marjaneh
Sep 5, 2019·International Journal of Molecular Sciences·Yaqi RenShuaiyu Wang
Nov 30, 2018·International Journal of Molecular Sciences·Teodora CosteaMaria-Magdalena Mocanu
Jun 27, 2019·Drug Development and Industrial Pharmacy·V R RanjithaV Ravishankar Rai
Oct 20, 2020·Expert Opinion on Drug Metabolism & Toxicology·Tariq IsmailCarmela Fimognari
Feb 23, 2020·Seminars in Cancer Biology·Sajad FakhriAnupam Bishayee
Jul 6, 2021·Frontiers in Cardiovascular Medicine·Graham ChakafanaKaren Sliwa

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Methods Mentioned

BETA
transfection

Software Mentioned

SPSS

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