Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

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
Download PDF
⟨ Previous Next ⟩

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

  1. Cardenas, C., Quesada, A. R. and Medina, M. A. (2011) Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene. PLoS One 6, e23407. https://doi.org/10.1371/journal.pone.0023407
  2. Cardenas, C., Quesada, A. R. and Medina, M. A. (2014) Insights on the antitumor effects of kahweol on human breast cancer: decreased survival and increased production of reactive oxygen species and cytotoxicity. Biochem. Biophys. Res. Commun. 447, 452-458. https://doi.org/10.1016/j.bbrc.2014.04.026
  3. Cavin, C., Holzhaeuser, D., Scharf, G., Constable, A., Huber, W. W. and Schilter, B. (2002) Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food Chem. Toxicol. 40, 1155-1163. https://doi.org/10.1016/S0278-6915(02)00029-7
  4. Garrido, C., Gurbuxani, S., Ravagnan, L. and Kroemer, G. (2001) Heat shock proteins: endogenous modulators of apoptotic cell death. Biochem. Biophys. Res. Commun. 286, 433-442.
  5. Giovannucci, E. (1998) Meta-analysis of coffee consumption and risk of colorectal cancer. Am. J. Epidemiol. 147, 1043-1052. https://doi.org/10.1093/oxfordjournals.aje.a009398
  6. Grivicich, I., Regner, A., Zanoni, C., Correa, L. P., Jotz, G. P., Henriques, J. A., Schwartsmann, G. and da Rocha, A. B. (2007) Hsp70 response to 5-fluorouracil treatment in human colon cancer cell lines. Int. J. Colorectal Dis. 22, 1201-1208. https://doi.org/10.1007/s00384-007-0307-x
  7. Gurbuxani S., Bruey J. M., Fromentin A., Larmonier N., Parcellier A., JääteläM., Martin F., Solary E., and Garrido C. (2001) Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells. Oncogene 20, 7478-7485. https://doi.org/10.1038/sj.onc.1204948
  8. Isshiki M., Ohta H., and Tamura H. (2013) Coffee reduces SULT1E1 expression in human colon carcinoma Caco-2 cells. Biol. Pharm. Bull. 36, 299-304. https://doi.org/10.1248/bpb.b12-00902
  9. Johnson S. M., Wang X., and Evers B. M. (2011) Triptolide inhibits proliferation and migration of colon cancer cells by inhibition of cell cycle regulators and cytokine receptors. J. Surg. Res. 168, 197-205. https://doi.org/10.1016/j.jss.2009.07.002
  10. Kim, H. G., Hwang, Y. P. and Jeong, H. G. (2009) Kahweol blocks STAT3 phosphorylation and induces apoptosis in human lung adenocarcinoma A549 cells. Toxicol. Lett. 187, 28-34. https://doi.org/10.1016/j.toxlet.2009.01.022
  11. Kim, J. A., Kim, Y., Kwon, B. M. and Han, D. C. (2013) The natural compound cantharidin induces cancer cell death through inhibition of heat shock protein 70 (HSP70) and Bcl-2-associated athanogene domain 3 (BAG3) expression by blocking heat shock factor 1 (HSF1) binding to promoters. J. Biol. Chem. 288, 28713-28726. https://doi.org/10.1074/jbc.M113.488346
  12. Larsson, S. C. and Wolk, A. (2007) Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology 132, 1740-1745. https://doi.org/10.1053/j.gastro.2007.03.044
  13. Lee, K. A., Chae, J. I. and Shim, J. H. (2012) Natural diterpenes from coffee, cafestol and kahweol induce apoptosis through regulation of specificity protein 1 expression in human malignant pleural mesothelioma. J. Biomed. Sci. 19, 60. https://doi.org/10.1186/1423-0127-19-60
  14. Lee, K. J. and Jeong, H. G. (2007) Protective effects of kahweol and cafestol against hydrogen peroxide-induced oxidative stress and DNA damage. Toxicol. Lett. 173, 80-87. https://doi.org/10.1016/j.toxlet.2007.06.008
  15. Oh, J. H., Lee, J. T., Yang, E. S., Chang, J. S., Lee, D. S., Kim, S. H., Choi, Y. H., Park, J. W. and Kwon, T. K. (2009) The coffee diterpene kahweol induces apoptosis in human leukemia U937 cells through down-regulation of Akt phosphorylation and activation of JNK. Apoptosis 14, 1378-1386. https://doi.org/10.1007/s10495-009-0407-x
  16. Rashmi, R., Kumar, S. and Karunagaran, D. (2004) Ectopic expression of Hsp70 confers resistance and silencing its expression sensitizes human colon cancer cells to curcumin-induced apoptosis. Carcinogenesis 25, 179-187.
  17. Sarto, C., Binz, P. A. and Mocarelli, P. (2000) Heat shock proteins in human cancer. Electrophoresis 21, 1218-1226. https://doi.org/10.1002/(SICI)1522-2683(20000401)21:6<1218::AID-ELPS1218>3.0.CO;2-H
  18. Schmitt E., Maingret L., Puig P. E., Rerole A. L., Ghiringhelli F., Hammann A., Solary E., Kroemer G., and Garrido C. (2006) Heat shock protein 70 neutralization exerts potent antitumor effects in animal models of colon cancer and melanoma. Cancer Res. 66, 4191-4197. https://doi.org/10.1158/0008-5472.CAN-05-3778
  19. Shiota, M., Kusakabe, H., Izumi, Y., Hikita, Y., Nakao, T., Funase, Y., Miura, K., and Iwao, H. (2010) Heat shock cognate protein 70 is essential for Akt signaling in endothelial function. Arterioscler. Thromb. Vasc. Biol. 30, 491-497. https://doi.org/10.1161/ATVBAHA.109.193631
  20. Singh, S. and Suri, A. (2014) Targeting the testis-specific heat-shock protein 70-2 (HSP70-2) reduces cellular growth, migration, and invasion in renal cell carcinoma cells. Tumour Biol. 35, 12695-12706. https://doi.org/10.1007/s13277-014-2594-5
  21. Spiller, M. A. (1984) The chemical components of coffee. Prog. Clin. Biol. Res. 158, 91-147.
  22. Stalder, R., Bexter, A., Wurzner, H. P. and Luginbuhl, H. (1990) A carcinogenicity study of instant coffee in Swiss mice. Food Chem. Toxicol. 28, 829-837. https://doi.org/10.1016/0278-6915(90)90056-S
  23. Takayama, S., Reed, J. C. and Homma, S. (2003) Heat-shock proteins as regulators of apoptosis. Oncogene 22, 9041-9047. https://doi.org/10.1038/sj.onc.1207114
  24. Um, H. J., Oh, J. H., Kim, Y. N., Choi, Y. H., Kim, S. H., Park, J. W. and Kwon, T. K. (2010) The coffee diterpene kahweol sensitizes TRAILinduced apoptosis in renal carcinoma Caki cells through down-regulation of Bcl-2 and c-FLIP. Chem. Biol. Interact. 186, 36-42. https://doi.org/10.1016/j.cbi.2010.04.013
  25. Vitaglione P., Fogliano V., and Pellegrini N. (2012) Coffee, colon function and colorectal cancer. Food Funct. 3, 916-922. https://doi.org/10.1039/c2fo30037k
  26. Wurzner, H. P., Lindstrom, E., Vuataz, L. and Luginbuhl, H. (1977) A 2-year feeding study of instant coffees in rats. II. Incidence and types of neoplasms. Food Cosmet. Toxicol. 15, 289-296. https://doi.org/10.1016/S0015-6264(77)80199-5
  27. Yang S., Chen J., Guo Z., Xu X. M., Wang L., Pei X. F., Yang J., Underhill C. B., and Zhang L. (2003) Triptolide inhibits the growth and metastasis of solid tumors. Mol. Cancer Ther. 2, 65-72.
  28. Yu, X., Bao, Z., Zou, J. and Dong, J. (2011) Coffee consumption and risk of cancers: a meta-analysis of cohort studies. BMC Cancer 11, 96. https://doi.org/10.1186/1471-2407-11-96
  29. Zhong, M. A., Zhang, H., Qi, X. Y., Lu, A. G., You, T. G., Gao, W., Guo, X. L., Zhou, Z. Q., Yang, Y. and Wang, C. J. (2011) ShRNAmediated gene silencing of heat shock protein 70 inhibits human colon cancer growth. Mol. Med. Rep. 4, 805-810.

Cited by

  1. The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3β-dependent threonine-286 phosphorylation in human colorectal cancer cells vol.95, 2016, https://doi.org/10.1016/j.fct.2016.07.008
  2. Terpenoids as anti-colon cancer agents – A comprehensive review on its mechanistic perspectives vol.795, 2017, https://doi.org/10.1016/j.ejphar.2016.12.008
  3. Influence of coffee and its components on breast cancer: A review vol.6, pp.10, 2016, https://doi.org/10.1016/S2222-1808(16)61140-4
  4. Kahweol from Coffee Induces Apoptosis by Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells vol.25, pp.3, 2017, https://doi.org/10.4062/biomolther.2016.114
  5. Kahweol inhibits adipogenesis of 3T3-L1 adipocytes through downregulation of PPARγ 2017, https://doi.org/10.1080/14786419.2017.1326039
  6. Aromatic polyketides from a caterpillar associated Alternaria sp. vol.58, pp.31, 2017, https://doi.org/10.1016/j.tetlet.2017.06.071
  7. Assessment of the Cytotoxic and Apoptotic Eἀects of Chaetominine in a Human Leukemia Cell Line vol.24, pp.2, 2016, https://doi.org/10.4062/biomolther.2015.093
  8. Kahweol inhibits lipid accumulation and induces Glucose-uptake through activation of AMP-activated protein kinase (AMPK) vol.50, pp.11, 2017, https://doi.org/10.5483/BMBRep.2017.50.11.031
  9. Polyphenols in Colorectal Cancer: Current State of Knowledge including Clinical Trials and Molecular Mechanism of Action vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/4154185
  10. Chemoprevention of Colorectal Cancer by Dietary Compounds vol.19, pp.12, 2018, https://doi.org/10.3390/ijms19123787
  11. An insight towards anticancer potential of major coffee constituents vol.44, pp.4, 2018, https://doi.org/10.1002/biof.1437
  12. The Impact of Coffee and Its Selected Bioactive Compounds on the Development and Progression of Colorectal Cancer In Vivo and In Vitro vol.23, pp.12, 2015, https://doi.org/10.3390/molecules23123309
  13. Chemopreventive effect of coffee against colorectal cancer and hepatocellular carcinoma vol.22, pp.1, 2015, https://doi.org/10.1080/10942912.2019.1593193
  14. Therapeutic potency of heat-shock protein-70 in the pathogenesis of colorectal cancer: current status and perspectives vol.97, pp.2, 2015, https://doi.org/10.1139/bcb-2018-0177
  15. Potent activity of bioconjugated peptide and selenium nanoparticles against colorectal adenocarcinoma cells vol.45, pp.9, 2015, https://doi.org/10.1080/03639045.2019.1634090
  16. Cafestol and Kahweol: A Review on Their Bioactivities and Pharmacological Properties vol.20, pp.17, 2015, https://doi.org/10.3390/ijms20174238
  17. Hsp70 inhibitors: Implications for the treatment of colorectal cancer vol.71, pp.12, 2015, https://doi.org/10.1002/iub.2157
  18. Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer vol.6, pp.11, 2015, https://doi.org/10.1001/jamaoncol.2020.3938
  19. Coffee in cancer chemoprevention: an updated review vol.17, pp.1, 2015, https://doi.org/10.1080/17425255.2021.1839412
  20. Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis vol.13, pp.1, 2015, https://doi.org/10.3390/nu13010088
  21. Kahweol Induces Apoptosis in Hepatocellular Carcinoma Cells by Inhibiting the Src/mTOR/STAT3 Signaling Pathway vol.22, pp.19, 2021, https://doi.org/10.3390/ijms221910509
  22. Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer vol.26, pp.21, 2015, https://doi.org/10.3390/molecules26216377
  23. Antioxidant and Anti-Inflammatory Activity of Coffee Brew Evaluated after Simulated Gastrointestinal Digestion vol.13, pp.12, 2015, https://doi.org/10.3390/nu13124368
  24. Antibacterial, Antiradical and Antiproliferative Potential of Green, Roasted, and Spent Coffee Extracts vol.12, pp.4, 2015, https://doi.org/10.3390/app12041938