Abstract
Capsaicin, the active component of chili pepper, has been reported to have antiproliferative and anti-inflammatory effects on a variety of cell lines. In the current study, we aimed to investigate the effects of capsaicin during HSC activation and maintenance. Activated and freshly isolated HSCs were treated with capsaicin. Proliferation was measured by incorporation of EdU. Cell cycle arrest and apoptosis were investigated using flow cytometry. The migratory response to chemotactic stimuli was evaluated by a modified Boyden chamber assay. Activation markers and inflammatory cytokines were determined by qPCR, immunocytochemistry, and flow cytometry. Our results show that capsaicin reduces HSC proliferation, migration, and expression of profibrogenic markers of activated and primary mouse HSCs. In conclusion, the present study shows that capsaicin modulates proliferation, migration, and activation of HSC in vitro.
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Kershenobich Stalnikowitz, D., & Weissbrod, A. B. (2003). Liver fibrosis and inflammation: A review. Annals of hepatology, 2(4), 159–163. PubMed PMID: 15115954.
Day, S. A., Lakner, A. M., Moore, C. C., Yen, M. H., Clemens, M. G., Wu, E. S., et al. (2011). Opioid-like compound exerts anti-fibrotic activity via decreased hepatic stellate cell activation and inflammation. Biochemical Pharmacology, 81(8), 996–1003. PubMed PMID: 21291870. Epub 2011/02/05. eng.
Van Beneden, K., Mannaerts, I., Pauwels, M., Van den Branden, C., & van Grunsven, L. A. (2013). HDAC inhibitors in experimental liver and kidney fibrosis. Fibrogenesis & Tissue Repair, 6(1), 1. PubMed PMID: 23281659. Pubmed Central PMCID: 3564760.
Iimuro, Y., & Brenner, D. A. (2008). Matrix metalloproteinase gene delivery for liver fibrosis. Pharmaceutical Research, 25(2), 249–258. PubMed PMID: 17577645. Pubmed Central PMCID: 2245995.
Solís-Herruzo, J., Solís-Muñoz, P., Muñoz-Yagüe, T., & García-Ruiz, I. (2011). Molecular targets in the design of antifibrotic therapy in chronic liver disease. Revista Espanola de Enfermedades Digestivas, 103(6), 310–323.
Kim, C. S., Park, W. H., Park, J. Y., Kang, J. H., Kim, M. O., Kawada, T., et al. (2004). Capsaicin, a spicy component of hot pepper, induces apoptosis by activation of the peroxisome proliferator-activated receptor gamma in HT-29 human colon cancer cells. Journal of Medicinal Food, 7(3), 267–273. PubMed PMID: 15383218. Epub 2004/09/24. eng.
Lin, C. H., Lu, W. C., Wang, C. W., Chan, Y. C., & Chen, M. K. (2013). Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Complementary and Alternative Medicine, 13, 46. PubMed PMID: 23433093. Pubmed Central PMCID: 3599796.
Bitencourt, S., de Mesquita, F. C., Caberlon, E., da Silva, G. V., Basso, B. S., Ferreira, G. A., et al. (2012). Capsaicin induces de-differentiation of activated hepatic stellate cell. Biochemistry and Cell Biology, 90(6), 683–690. PubMed PMID: 22905849. Epub 2012/08/22. eng.
Guimaraes, E. L., Empsen, C., Geerts, A., & van Grunsven, L. A. (2010). Advanced glycation end products induce production of reactive oxygen species via the activation of NADPH oxidase in murine hepatic stellate cells. Journal of Hepatology, 52(3), 389–397.
Mannaerts, I., Nuytten, N. R., Rogiers, V., Vanderkerken, K., van Grunsven, L. A., & Geerts, A. (2010). Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo. Hepatology, 51(2), 603–614.
Cossarizza, A., Baccarani-Contri, M., Kalashnikova, G., & Franceschi, C. (1993). A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochemical and Biophysical Research Communications, 197(1), 40–45. PubMed PMID: 8250945. Epub 1993/11/30. eng.
Reers, M., Smiley, S. T., Mottola-Hartshorn, C., Chen, A., Lin, M., & Chen, L. B. (1995). Mitochondrial membrane potential monitored by JC-1 dye. Methods in Enzymology, 260, 406–417. PubMed PMID: 8592463. Epub 1995/01/01. eng.
Borojevic, R., Guaragna, R. M., Margis, R., & Dutra, H. S. (1990). In vitro induction of the fat-storing phenotype in a liver connective tissue cell line-GRX. In Vitro Cellular & Developmental Biology, 26(4), 361–368. PubMed PMID: 2188940. Epub 1990/04/01. eng.
Souza, I. C., Martins, L. A., Coelho, B. P., Grivicich, I., Guaragna, R. M., Gottfried, C., et al. (2008). Resveratrol inhibits cell growth by inducing cell cycle arrest in activated hepatic stellate cells. Molecular and Cellular Biochemistry, 315(1–2), 1–7. PubMed PMID: 18454344. Epub 2008/05/06. eng.
Teodoro, A. J., Perrone, D., Martucci, R. B., & Borojevic, R. (2009). Lycopene isomerisation and storage in an in vitro model of murine hepatic stellate cells. European Journal of Nutrition, 48(5), 261–268. PubMed PMID: 19533199. Epub 2009/06/18. eng.
Braganca de Moraes, C. M., Melo, D. A., Santos, R. C., Bitencourt, S., Mesquita, F. C., Santos de Oliveira, F. D., et al. (2012). Antiproliferative effect of catechin in GRX cells. Biochemistry and Cell Biology, 90(4), 575–584. PubMed PMID: 22574829. Epub 2012/05/12. eng.
Gupta, S. C., Kim, J. H., Prasad, S., & Aggarwal, B. B. (2010). Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer and Metastasis Reviews, 29(3), 405–434. PubMed PMID: 20737283. Pubmed Central PMCID: 2996866. Epub 2010/08/26. eng.
Surh, Y. J. (2002). Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food and Chemical Toxicology, 40(8), 1091–1097. PubMed PMID: 12067569. Epub 2002/06/18. eng.
Takahata, K., Chen, X., Monobe, K., & Tada, M. (1999). Growth inhibition of capsaicin on HeLa cells is not mediated by intracellular calcium mobilization. Life Sciences, 64(13), PL165–PL171. PubMed PMID: 10210280. Epub 1999/04/21. eng.
Hsu, C. L., & Yen, G. C. (2007). Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. Journal of Agriculture and Food Chemistry, 55(5), 1730–1736. PubMed PMID: 17295509. Epub 2007/02/14. eng.
Zhang, F., Kong, D., Lu, Y., & Zheng, S. (2012). Peroxisome proliferator-activated receptor-gamma as a therapeutic target for hepatic fibrosis: From bench to bedside. Cellular and Molecular Life Sciences, 70(2), 259–276. PubMed PMID: 22699820. Epub 2012/06/16. Eng.
van Engeland, M., Nieland, L. J., Ramaekers, F. C., Schutte, B., & Reutelingsperger, C. P. (1998). Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry, 31(1), 1–9. PubMed PMID: 9450519. Epub 1998/02/05. eng.
Ly, J. D., Grubb, D. R., & Lawen, A. (2003). The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis, 8(2), 115–128. PubMed PMID: 12766472. Epub 2003/05/27. eng.
Friedman, S. L. (2008). Mechanisms of hepatic fibrogenesis. Gastroenterology, 134(6), 1655–1669. PubMed PMID: WOS:000255771200003. English.
Yang, C., Zeisberg, M., Mosterman, B., Sudhakar, A., Yerramalla, U., Holthaus, K., et al. (2003). Liver fibrosis: insights into migration of hepatic stellate cells in response to extracellular matrix and growth factors. Gastroenterology, 124(1), 147–159.
Friedman, S. L. (2008). Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiological Reviews, 88(1), 125–172. PubMed PMID: 18195085. Pubmed Central PMCID: 2888531.
Kong, X., Horiguchi, N., Mori, M., & Gao, B. (2012). Cytokines and STATs in Liver Fibrosis. Frontiers in physiology, 3, 69. PubMed PMID: 22493582. Pubmed Central PMCID: 3318231.
Watford, W. T., Moriguchi, M., Morinobu, A., & O’Shea, J. J. (2003). The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine & Growth Factor Reviews, 14(5), 361–368. PubMed PMID: 12948519. Epub 2003/09/02. eng.
Saile, B., Eisenbach, C., Dudas, J., El-Armouche, H., & Ramadori, G. (2004). Interferon-gamma acts proapoptotic on hepatic stellate cells (HSC) and abrogates the antiapoptotic effect of interferon-alpha by an HSP70-dependant pathway. European Journal of Cell Biology, 83(9), 469–476. PubMed PMID: 15540463. Epub 2004/11/16. eng.
Li, J. T., Liao, Z. X., Ping, J., Xu, D., & Wang, H. (2008). Molecular mechanism of hepatic stellate cell activation and antifibrotic therapeutic strategies. Journal of Gastroenterology, 43(6), 419–428. PubMed PMID: 18600385. Epub 2008/07/05. eng.
Marra, F. (2002) Chemokines in liver inflammation and fibrosis. Frontiers in Bioscience, 7, d1899–d1914. PubMed PMID: 12161342. Epub 2002/08/06. eng.
Acknowledgments
This work was supported by CAPES/DGU (BEX 4426/10-0) Grant of the Brazilian Ministry of Science and Technology and Secretaria de Estado de Universidades (PHB2008-0080-PC) Grant of the Spanish Ministry of Science and Innovation. SB is receipt of a fellowship from CAPES. LAvG is supported by the Vrije Universiteit Brussels.
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Leo Adrianus van Grunsven and Jarbas Oliveira have contributed equally to this study.
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Bitencourt, S., Mesquita, F., Basso, B. et al. Capsaicin Modulates Proliferation, Migration, and Activation of Hepatic Stellate Cells. Cell Biochem Biophys 68, 387–396 (2014). https://doi.org/10.1007/s12013-013-9719-0
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DOI: https://doi.org/10.1007/s12013-013-9719-0