DOI QR코드

DOI QR Code

Antifibrotic Effect of Curcumin in TGF-β1-Induced Myofibroblasts from Human Oral Mucosa

  • Zhang, Shan-Shan (Department of Stomatology, Second Xiangya Hospital, Central South University) ;
  • Gong, Zhao-Jian (Department of Stomatology, Second Xiangya Hospital, Central South University) ;
  • Li, Wen-Hui (Department of Stomatology, Second Xiangya Hospital, Central South University) ;
  • Wang, Xiao (Department of Stomatology, Second Xiangya Hospital, Central South University) ;
  • Ling, Tian-You (Department of Stomatology, Second Xiangya Hospital, Central South University)
  • Published : 2012.01.31

Abstract

Background: Myofibroblasts play an important role in the development of oral submucous fibrosis (OSF). In the current study, we investigate the effect of curcumin on growth and apoptosis of myofibroblasts derived from human oral mucosa. Methods: Myofibroblasts were generated by incubating fibroblasts, obtained from human oral mucosa, with transforming growth factor-${\beta}1$ (TGF-${\beta}1$). MTT, PI staining, and FACS assays were used to investigate curcumin's effect on proliferation and cell cycle of fibroblasts and myofibroblasts. Annexin V/PI binding and FACS assays were used to examine apoptosis of myofibroblasts, Western blotting to determine the levels of Bcl-2 and Bax, and enzyme-linked immunosorbant assay was employed to examine the levels of collagen type I and III in the supernatants of myofibroblasts. Results: Curcumin inhibits proliferation of fibroblasts and myofibroblasts; it also disturbs the cell cycle, induces apoptosis and decreases the generation of collagen type I and III in myofibroblasts, which are more sensitive to its effects than fibroblasts. Curcumin induces apoptosis in myofibroblasts by down-regulating the Bcl-2/ Bax ratio. Conclusion: Our results demonstrate the antifibrotic effect of curcumin in vitro. It may therefore be a candidate for the treatment of OSF.

Keywords

References

  1. Angadi PV, Kale AD, Hallikerimath S (2011). Evaluation of myofibroblasts in oral submucous fibrosis: correlation with disease severity. J Oral Pathol Med, 40, 208-13. https://doi.org/10.1111/j.1600-0714.2010.00995.x
  2. Atsumi T, Tonosaki K, Fujisawa S (2006). Induction of early apoptosis and ROS-generation activity in human gingival fibroblasts (HGF) and human submandibular gland carcinoma (HSG) cells treated with curcumin. Arch Oral Biol, 51, 913-21. https://doi.org/10.1016/j.archoralbio.2006.03.016
  3. Boucher BJ, Mannan N (2002). Metabolic effects of the consumption of Areca catechu. Addict Biol, 7, 103-10. https://doi.org/10.1080/13556210120091464
  4. Bruck R, Ashkenazi M, Weiss S, et al (2007). Prevention of liver cirrhosis in rats by curcumin. Liver Int, 27, 373-83. https://doi.org/10.1111/j.1478-3231.2007.01453.x
  5. Chen A, Xu J (2005). Activation of PPAR{gamma} by curcumin inhibits Moser cell growth and mediates suppression of gene expression of cyclin D1 and EGFR. Am J Physiol Gastrointest Liver Physiol, 288, G447-56. https://doi.org/10.1152/ajpgi.00209.2004
  6. Chen A, Xu J, Johnson AC (2006). Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene, 25, 278-87. https://doi.org/10.1038/sj.onc.1209019
  7. Choudhuri T, Pal S, Das T, Sa G (2005). Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem, 280, 20059-68. https://doi.org/10.1074/jbc.M410670200
  8. Divya CS, Pillai MR (2006). Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis. Mol Carcinog, 45, 320-32. https://doi.org/10.1002/mc.20170
  9. Elledge SJ (1996). Cell cycle checkpoints: preventing an identity crisis. Science, 274, 1664-72. https://doi.org/10.1126/science.274.5293.1664
  10. Fedorowicz Z, Chan Shih-Yen E, Dorri M, et al (2008). Interventions for the management of oral submucous fibrosis. Cochrane Database Syst Rev, 8, CD007156.
  11. Gabbiani G (2003). The myofibroblast in wound healing and fibrocontractive diseases. J Pathol, 200, 500-3. https://doi.org/10.1002/path.1427
  12. Goel A, Jhurani S, Aggarwal BB (2008). Multi-targeted therapy by curcumin: how spicy is it? Mol Nutr Food Res, 52, 1010-30. https://doi.org/10.1002/mnfr.200700354
  13. Hinz B, Phan SH, Thannickal VJ, et al (2007). The myofibroblast: one function, multiple origins. Am J Pathol, 170, 1807-16. https://doi.org/10.2353/ajpath.2007.070112
  14. International Agency for Research on Cancer (2005). WHO classification of tumors: pathology and genetics of head and neck tumors. IARC Press, Lyon.
  15. Jackson JK, Higo T, Hunter WL, Burt HM (2006). The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm Res, 55, 168-75. https://doi.org/10.1007/s00011-006-0067-z
  16. Jiang MC, Yang-Yen HF, Yen JJ, Lin JK (1996). Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer, 26, 111-20. https://doi.org/10.1080/01635589609514468
  17. Jiang X, Hu J (2009). Drug treatment of oral submucous fibrosis: a review of the literature. J Oral Maxillofac Surg, 67, 1510-5. https://doi.org/10.1016/j.joms.2008.12.056
  18. Kerr AR, Warnakulasuriya S, Mighell AJ, et al (2011). A systematic review of medical interventions for oral submucous fibrosis and future research opportunities. Oral Dis, 1, 42-57.
  19. Lin YL, Lin CY, Chi CW, Huang YT (2009). Study on antifibrotic effects of curcumin in rat hepatic stellate cells. Phytother Res, 23, 927-32. https://doi.org/10.1002/ptr.2764
  20. Liu HS, Ke CS, Cheng HC, Huang CY, Su CL (2011). Curcumininduced mitotic spindle defect and cell cycle arrest in human bladder cancer cells occurs partly through inhibition of Aurora A. Mol Pharmacol, 80, 638-46. https://doi.org/10.1124/mol.111.072512
  21. Miyashita T, Krajewski S, Krajewska M, et al (1994). Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene, 9, 1799-805.
  22. Miyashita T, Reed JC (1995). Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell, 80, 293-9. https://doi.org/10.1016/0092-8674(95)90412-3
  23. Montopoli M, Ragazzi E, Froldi G, Caparrotta L (2009). Cellcycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells. Cell Prolif, 42, 195-206. https://doi.org/10.1111/j.1365-2184.2009.00585.x
  24. Osawa T (2007). Nephroprotective and hepatoprotective effects of curcuminoids. Adv Exp Med Biol, 595, 407-23. https://doi.org/10.1007/978-0-387-46401-5_18
  25. Powell DW, Mifflin RC, Valentich JD, et al (1999). Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol, 277, C1-9. https://doi.org/10.1152/ajpcell.1999.277.1.C1
  26. Puliyappadamba VT, Cheriyan VT, Thulasidasan AK, et al (2010). Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its downregulation by curcumin is independent. Mol Cancer, 9, 220. https://doi.org/10.1186/1476-4598-9-220
  27. Rajalalitha P, Vali S (2005). Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder. J Oral Pathol Med, 34, 321-8. https://doi.org/10.1111/j.1600-0714.2005.00325.x
  28. Rivera-Espinoza Y, Muriel P (2009). Pharmacological actions of curcumin in liver diseases or damage. Liver Int, 29, 1457-66. https://doi.org/10.1111/j.1478-3231.2009.02086.x
  29. Singh M, Chaudhary AK, Pandya S, et al (2010). Morphometric analysis in potentially malignant head and neck lesions: oral submucous fibrosis. Asian Pac J Cancer Prev, 11, 257-60.
  30. Smith MR, Gangireddy SR, Narala VR, et al (2010). Curcumin inhibits fibrosis-related effects in IPF fibroblasts and in mice following bleomycin-induced lung injury. Am J Physiol Lung Cell Mol Physiol, 298, L616-25. https://doi.org/10.1152/ajplung.00002.2009
  31. Strimpakos AS, Sharma RA (2008). Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal, 10, 511-45. https://doi.org/10.1089/ars.2007.1769
  32. Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S (2006). Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol, 42, 561-8. https://doi.org/10.1016/j.oraloncology.2005.08.005
  33. Utsunomiya H, Tilakaratne WM, Oshiro K, et al (2005). Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization. J Oral Pathol Med, 34, 498-507. https://doi.org/10.1111/j.1600-0714.2005.00339.x
  34. Venkatesan N, Punithavathi D, Babu M (2007). Protection from acute and chronic lung diseases by curcumin. Adv Exp Med Biol, 595, 379-405. https://doi.org/10.1007/978-0-387-46401-5_17
  35. Watsky MA, Weber KT, Sun Y, Postlethwaite A (2010). New insights into the mechanism of fibroblast to myofibroblast transformation and associated pathologies. Int Rev Cell Mol Biol, 282, 165-92. https://doi.org/10.1016/S1937-6448(10)82004-0
  36. Wu SH, Hang LW, Yang JS, et al (2010). Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways. Anticancer Res, 30, 2125-33.

Cited by

  1. Curcumin Inhibits TGF-β1-Induced MMP-9 and Invasion through ERK and Smad Signaling in Breast Cancer MDA-MB-231 Cells vol.13, pp.11, 2012, https://doi.org/10.7314/APJCP.2012.13.11.5709
  2. Myofibroblast Differentiation: Main Features, Biomedical Relevance, and the Role of Reactive Oxygen Species vol.21, pp.5, 2014, https://doi.org/10.1089/ars.2013.5724
  3. Intravenous curcumin efficacy on healing and scar formation in rabbit ear wounds under nonischemic, ischemic, and ischemia-reperfusion conditions vol.22, pp.6, 2014, https://doi.org/10.1111/wrr.12231
  4. Anti-carcinogenic and Anti-bacterial Properties of Selected Spices: Implications in Oral Health vol.4, pp.4, 2015, https://doi.org/10.7762/cnr.2015.4.4.209
  5. Evaluating the ameliorative potential of plant flavonoids and their nanocomposites in bleomycin induced idiopathic pulmonary fibrosis vol.3, pp.7, 2016, https://doi.org/10.7603/s40730-016-0032-6
  6. Linn and asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts vol.8, pp.2, 2016, https://doi.org/10.1111/jicd.12208
  7. Effect of curcumin on the expression of p53, transforming growth factor-β, and inducible nitric oxide synthase in oral submucous fibrosis: A pilot study vol.8, pp.4, 2016, https://doi.org/10.1111/jicd.12252
  8. Modulation of tumor microenvironment by chemopreventive natural products vol.1401, pp.1, 2017, https://doi.org/10.1111/nyas.13395
  9. Model for Radiation-Induced Fibrosis vol.189, pp.3, 2018, https://doi.org/10.1667/RR14926.1
  10. Curcumin ameliorates monosodium urate-induced gouty arthritis through Nod-like receptor 3 inflammasome mediation via inhibiting nuclear factor-kappa B signaling vol.120, pp.4, 2018, https://doi.org/10.1002/jcb.27969