Effect of tagitinin C isolated from Tithonia diversifoli (Hemsley) A Gray on migration activity and TGF-β1 levels on keloid fibroblast


Elvira Santi(1*), Mae Sri Hartati Wahyuningsih(2), Arief Budiyanto(3)

(1) Study Program of Basic Medical and Biomedical Sciences, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta
(2) Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta
(3) Department of Dermatovenerology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author


Keloid is the formation of excessive scar tissue characterized by fibroblast hiperproliferations and collagen deposits that are similar with cancer cells. Tagitinin C is proven can inhibit proliferation and deposition of keloids collagen fibroblast. However, the mechanism of action of tagitinin C in migration activities and TGF-β1 levels of keloid fibroblasts has not been proved, yet. This study aimed to investigate the effects of tagitinin C isolated from Tithonia diversifoli (Hemsley) on migration activity and TGF-β1 expression of keloid fibroblast. This was quasi experimental study with post test only controlled group design using keloid fibroblasts isolated from keloid patients. The migration activity were performed by scratch assay and TGF-β1 levels were measured using an ELISA kits. Isolate tagitinin C was more active inhibit fibroblast keloid migration compare to the control groups (p<0.05) after 48 h incubation. TGF-β1 levels after incubation with isolate tagitinin C was lower then control group (p<0.05). In conclusion, isolate tagitinin C can inhibit migration and reduce TGF-β1 levels on keloid fibroblast


Keloid fibroblast; Proliferation; Tagitinin C; TGF-β1 Level

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  1. Mutalik S. Treatment of keloids and hypertrophic scars. J Dermatol Venereol Leprol 2005; 71:3-8. https://doi.org/10.4103/0378-6323.13777
  2. Seo BF, Lee JY, Jung SN. Models of abnormal scarring. Biomed Res Int 2013; 2013:423147. https://doi.org/10.1155/2013/423147
  3. Wood F, Rea S, Tuckerman J, Fowler B, Peng L. Intervention for treating keloid disease Protocol. Cochrane Data Base of Systematic Reviews 2009; 1-9. https://doi.org/10.1002/14651858.CD006805.pub2
  4. Nemeth, Albert J. Keloids and hypertropic scars. J Dermatol Surg Oncol 1993; 19: 738-46. https://doi.org/10.1111/j.1524-4725.1993.tb00418.x
  5. Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J. Am Coll of Surg 2008; 206(4):31-40. https://doi.org/10.1016/j.jamcollsurg.2007.12.001
  6. Wahyuningsih MSH, Wirohadidjojo YW, Hidayat R, Sadid A. Antifibrotic effect of standardized ethanol extract of Tithonia diversifolia (Hemsley) A. Gray on keloid fibroblasts. Int J Pharmacog Phytochem Res 2015; 7(4):642-7.
  7. Wahyuningsih MSH, Wijayanti MA, Budiyanto A, Hanafi M. Isolation and identification of potential cytotoxic compound from Tithonia diversifolia (Hemsley) A. Gray. leaves. Int J Pharm Pharm Sci 2015; 7(6):298-301.
  8. Ranti I, Wahyuningsih MSH, Wirohadidjojo YW. The antifibrotic effect of isolate tagitinin C from [Tithonia diversifolia (Hemsley) A. Gray] on keloid fibroblast cell. Pan Afr Med J 2018; 30:264. https://doi.org/10.11604/pamj.2018.30.264.9994
  9. Freshney RI. Culture of animal cells: a manual of basic technique 4th ed. New York: Willey-Liss, 2000.
  10. Le AD, Zhang Q, Wu Y, Messadi DV, Akhondzadeh A, Nguyen AL et al. Elevated vascular endothelial growth factor in keloids: relevance to tissue fibrosis. Cells Tissues Organs 2004; 176:87-94. https://doi.org/10.1159/000075030
  11. Liang Y, Niederstrasser H, Edwards M, Jackson CE, Cooper JA. Distinct roles for CARMIL isoforms in cell migration. J Mol Biol Cell. 2009; 20(24): 5290-305. https://doi.org/10.1091/mbc.e08-10-1071
  12. Straatman K. Wound healing assay. J Mol Biol Cells 2008; 10: 1-4.
  13. Fujiwara M, Muragaki Y and Ooshima. Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. Br J Dermatol. 2005; 153: 295-200. https://doi.org/10.1111/j.1365-2133.2005.06698.x
  14. Chen Y, Abraham DJ, Shi-Wen X, Pearson JD, Black CM, Lyons KM, et al. CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin. Mol Biol Cell. 2004; 15: 5635-46. https://doi.org/10.1091/mbc.e04-06-0490
  15. Xuan YH, Huang BB, Tian HS, Chi LS, Duan YM, Wang X, et al. High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. J PLoS ONE 2014; 9(9):1-14. https://doi.org/10.1371/journal.pone.0108182
  16. Dachlan I. Pengaruh 5α-oleandrin isolasi dari daun kembang mentega (Nerium indicum Mill) sebagai obat antikeloid kajian in vitro pada sel fibroblas keloid. [Disertasi]. Yogyakarta: Universitas Gadjah Mada, 2015.
  17. Syed F, Sherris D, Paus R, Varmeh S, Pandolfi PP, Bayat A. Keloid disease can be inhibited by antagonizing excessive mTOR signaling with a novel dual TORC1/1 inhibitor. Am J Pathol 2012; 181(5): 1642-56. https://doi.org/10.1016/j.ajpath.2012.08.006
  18. Santi E. Effect of isolate tagitinin C from Tithonia diversifolia [Hemsley) A Gray] on migration activities and expressions of TGF-β keloid fibroblasts. [Thesis]. Yogyakarta: Faculty of Medicine, Public Health and Nursing, Universitas GadjahMada, 2017.
  19. Yang L, Pang Y, Moses HL. TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol 2010; 31:220-227. https://doi.org/10.1016/j.it.2010.04.002
  20. Lasek W, Jakóbisiak M, Gołab J. Natural mechanisms protecting against cancer. Immunol Lett 2003; 90(2-3):103-22. https://doi.org/10.1016/j.imlet.2003.08.005
  21. Razak FA, Rahman MR, Bakri MM. Evaluation of wound closure activity of Nigella sativa, Melastoma malabathricum, Pluchea indica, and Piper saramentosum extracts on scratched monolayer of human gingival fibroblasts. Evidence-Based Compl Altern Med 2014; 9:1-10. https://doi.org/10.1155/2014/190342
  22. Park SY, Park JY, Kim CH, Kang SV, Kim JH, Bark KM, et al. Effects of Xanthium stramarium and Psoralencotylifolia extracts combined with UVA1 irradiation on the cell proliferation and TGF-β1 expression of keloid fibroblasts. Ann Dermatol 2013; 25(3):304-9. https://doi.org/10.5021/ad.2013.25.3.304

DOI: https://doi.org/10.19106/JMedSci005103201901

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Journal of the Medical Sciences (Berkala Ilmu Kedokteran) by  Universitas Gadjah Mada is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.