Biomolecules & Therapeutics

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

DOI QR Code

4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling

  • Kim, Sang-Cheol (Department of Medicine, Jeju National University School of Medicine) ;
  • Kang, Jung-Il (Department of Medicine, Jeju National University School of Medicine) ;
  • Hyun, Jin-Won (Department of Medicine, Jeju National University School of Medicine) ;
  • Kang, Ji-Hoon (Department of Medicine, Jeju National University School of Medicine) ;
  • Koh, Young-Sang (Department of Medicine, Jeju National University School of Medicine) ;
  • Kim, Young-Heui (R&D Center, Bioland Ltd.) ;
  • Kim, Ki-Ho (R&D Center, Bioland Ltd.) ;
  • Ko, Ji-Hee (Department of Medicine, Jeju National University School of Medicine) ;
  • Yoo, Eun-Sook (Department of Medicine, Jeju National University School of Medicine) ;
  • Kang, Hee-Kyoung (Department of Medicine, Jeju National University School of Medicine)
  • Received : 2016.01.06
  • Accepted : 2016.11.15
  • Published : 2017.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-${\beta}$ (TGF-${\beta}$) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-${\beta}$ signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-${\beta}$-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-${\beta}1$-induced G1/G0 phase arrest and TGF-${\beta}1$-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-${\beta}1$-induced canonical pathway. We observed that ERK phosphorylation by TGF-${\beta}1$ was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-${\beta}1$-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-${\beta}1$-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-${\beta}1$-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-${\beta}1$-induced cell cycle arrest.

Keywords

References

  1. Bascom, C. C., Sipes, N. J., Coffey, R. J. and Moses, H. L. (1989) Regulation of epithelial cell proliferation by transforming growth factors. J. Cell. Biochem. 39, 25-32. https://doi.org/10.1002/jcb.240390104
  2. Bradford, L. W. (1976) Problems of ethics and behavior in the forensic sciences. J. Forensic. Sci. 21, 763-768.
  3. Carmona-Cuenca, I., Roncero, C., Sancho, P., Caja, L., Fausto, N., Fernandez, M. and Fabregat, I. (2008) Upregulation of the NADPH oxidase NOX4 by TGF-${\beta}$ in hepatocytes is required for its proapoptotic activity. J. Hepatol. 49, 965-976. https://doi.org/10.1016/j.jhep.2008.07.021
  4. Carrillo, M. C., Kanai, S., Nokubo, M. and Kitani, K. (1991) (-) deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats. Life Sci. 48, 517-521. https://doi.org/10.1016/0024-3205(91)90466-O
  5. Cheng, G., Cao, Z., Xu, X., van Meir, E. G. and Lambeth, J. D. (2001) Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene 269, 131-140. https://doi.org/10.1016/S0378-1119(01)00449-8
  6. Datta, P. K., Blake, M. C. and Moses, H. L. (2000) Regulation of plasminogen activator inhibitor-1 expression by transforming growth factor-${\beta}$-induced physical and functional interactions between smads and Sp1. J. Biol. Chem. 275, 40014-40019. https://doi.org/10.1074/jbc.C000508200
  7. Ellenrieder, V. (2008) $TGF{\beta}$ regulated gene expression by Smads and Sp1/KLF-like transcription factors in cancer. Anticancer Res. 28, 1531-1539.
  8. Foitzik, K., Lindner, G., Mueller-Roever, S., Maurer, M., Botchkareva, N., Botchkarev, V., Handjiski, B., Metz, M., Hibino, T., Soma, T., Dotto, G. P. and Paus, R. (2000) Control of murine hair follicle regression (catagen) by TGF-${\beta}1$ in vivo. FASEB J. 14, 752-760. https://doi.org/10.1096/fasebj.14.5.752
  9. Foitzik, K., Paus, R., Doetschman, T. and Dotto, G. P. (1999) The TGF-${\beta}2$ isoform is both a required and sufficient inducer of murine hair follicle morphogenesis. Dev. Biol. 212, 278-289. https://doi.org/10.1006/dbio.1999.9325
  10. Guyton, K. Z., Liu, Y., Gorospe, M., Xu, Q. and Holbrook, N. J. (1996) Activation of mitogen-activated protein kinase by $H_2O_2$. Role in cell survival following oxidant injury. J. Biol. Chem. 271, 4138-4142. https://doi.org/10.1074/jbc.271.8.4138
  11. Hong, Y. H., Peng, H. B., La Fata, V. and Liao, J. K. (1997) Hydrogen peroxide-mediated transcriptional induction of macrophage colonystimulating factor by TGF-${\beta}1$. J. Immunol. 159, 2418-2423.
  12. Hu, P. P., Shen, X., Huang, D., Liu, Y., Counter, C. and Wang, X. F. (1999) The MEK pathway is required for stimulation of p21 (WAF1/CIP1) by transforming growth factor-${\beta}$. J. Biol. Chem. 274, 35381-35387. https://doi.org/10.1074/jbc.274.50.35381
  13. Hyun, S., Kim, M. S., Song, Y. S., Bak, Y., Ham, S. Y., Lee, D. H., Hong, J. and Yoon, D. Y. (2015) Peroxisome proliferator-activated receptor-gamma agonist 4-O-Methylhonokiol induces apoptosis by triggering the intrinsic apoptosis pathway and inhibiting the PI3K/Akt survival pathway in SiHa human cervical cancer cells. J. Microbiol. Biotechnol. 25, 334-342. https://doi.org/10.4014/jmb.1411.11073
  14. Inui, S., Fukuzato, Y., Nakajima, T., Yoshikawa, K. and Itami, S. (2002) Androgen-inducible TGF-${\beta}1$ from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth. FASEB J. 16, 1967-1969. https://doi.org/10.1096/fj.02-0043fje
  15. Kim, S. C., Kang, J. I., Kim, M. K., Boo, H. J., Park, D. B., Lee, Y. K., Kang, J. H., Yoo, E. S., Kim, Y. H. and Kang, H. K. (2011) The hair growth promoting effect of 4-O-Methylhonokiol. Eur..J. Dermatol. 21, 1012-1014.
  16. Krishan, A. (1975) Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. J. Cell Biol. 66, 188-193. https://doi.org/10.1083/jcb.66.1.188
  17. Lee, N. J., Oh, J. H., Ban, J. O., Shim, J. H., Lee, H. P., Jung, J. K., Ahn, B. W., Yoon, D. Y., Han, S. B., Ham, Y. W. and Hong, J. T. (2013) 4-O-Methylhonokiol, a $PPAR{\gamma}$ agonist, inhibits prostate tumour growth: p21-mediated suppression of NF-${\kappa}B$ activity. Br. J. Pharmacol. 168, 1133-1145. https://doi.org/10.1111/j.1476-5381.2012.02235.x
  18. Lee, Y. J., Choi, I. S., Park, M. H., Lee, Y. M., Song, J. K., Kim, Y. H., Kim, K. H., Hwang, D. Y., Jeong, J. H., Yun, Y. P., Oh, K. W., Jung, J. K., Han, S. B. and Hong, J. T. (2011) 4-O-Methylhonokiol attenuates memory impairment in presenilin 2 mutant mice through reduction of oxidative damage and inactivation of astrocytes and the ERK pathway. Free Radic. Biol. Med. 50, 66-77. https://doi.org/10.1016/j.freeradbiomed.2010.10.698
  19. Lee, Y. K., Choi, I. S., Kim, Y. H., Kim, K. H., Nam, S. Y., Yun, Y. W., Lee, M. S., Oh, K. W. and Hong, J. T. (2009a) Neuriteoutgrowth effect of 4-O-Methylhonokiol by induction of neurotrophic factors through ERK activation. Neurochem. Res. 34, 2251-2260. https://doi.org/10.1007/s11064-009-0024-7
  20. Lee, Y. K., Yuk, D. Y., Kim, T. I., Kim, Y. H., Kim, K. T., Kim, K. H., Lee, B. J., Nam, S. Y. and Hong, J. T. (2009b) Protective effect of the ethanol extract of Magnolia officinalis and 4-O-Methylhonokiol on scopolamine-induced memory impairment and the inhibition of acetylcholinesterase activity. J. Nat. Med. 63, 274-282. https://doi.org/10.1007/s11418-009-0330-z
  21. Li, C., Garland, J. M. and Kumar, S. (2001) Re: Role of transforming growth factor-${\beta}$ signaling in cancer. J. Natl. Cancer Inst. 93, 555-556. https://doi.org/10.1093/jnci/93.7.555
  22. Li, C. Y., Suardet, L. and Little, J. B. (1995) Potential role of WAF1/Cip1/p21 as a mediator of TGF-${\beta}$ cytoinhibitory effect. J. Biol. Chem. 270, 4971-4974. https://doi.org/10.1074/jbc.270.10.4971
  23. Massague, J. and Wotton, D. (2000) Transcriptional control by the TGF-${\beta}$/Smad signaling system. EMBO J. 19, 1745-1754. https://doi.org/10.1093/emboj/19.8.1745
  24. Misra, H. P. and Fridovich, I. (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem. 247, 3170-3175.
  25. Moustakas, A., Pardali, K., Gaal, A. and Heldin, C. H. (2002) Mechanisms of TGF-${\beta}$ signaling in regulation of cell growth and differentiation. Immunol. Lett. 82, 85-91. https://doi.org/10.1016/S0165-2478(02)00023-8
  26. Oh, J. H., Kang, L. L., Ban, J. O., Kim, Y. H., Kim, K. H., Han, S. B. and Hong, J. T. (2009) Anti-inflammatory effect of 4-O-Methylhonokiol, compound isolated from Magnolia officinalis through inhibition of NF-${\kappa}B$. Chem. Biol. Interact. 180, 506-514. https://doi.org/10.1016/j.cbi.2009.03.014
  27. Palazuelos, J., Klingener, M. and Aguirre, A. (2014) $TGF{\beta}$ signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3/4/FoxO1/Sp1. J. Neurosci. 34, 7917-7930. https://doi.org/10.1523/JNEUROSCI.0363-14.2014
  28. Pardali, K., Kurisaki, A., Moren, A., ten Dijke, P., Kardassis, D. and Moustakas, A. (2000) Role of Smad proteins and transcription factor Sp1 in p21 (Waf1/Cip1) regulation by transforming growth factor-${\beta}$. J. Biol. Chem. 275, 29244-29256. https://doi.org/10.1074/jbc.M909467199
  29. Paus, R., Muller-Rover, S., Van Der Veen, C., Maurer, M., Eichmuller, S., Ling, G., Hofmann, U., Foitzik, K., Mecklenburg, L. and Handjiski, B. (1999) A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. J. Invest. Dermatol. 113, 523-532. https://doi.org/10.1046/j.1523-1747.1999.00740.x
  30. Peshavariya, H. M., Chan, E. C., Liu, G. S., Jiang, F. and Dusting, G. J. (2014) Transforming growth factor-${\beta}1$ requires NADPH oxidase 4 forangiogenesis in vitro and in vivo. J. Cell. Mol. Med. 18, 1172-1183. https://doi.org/10.1111/jcmm.12263
  31. Reagan-Shaw, S., Breur, J. and Ahmad, N. (2006) Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes. Mol. Cancer Ther. 5, 418-429. https://doi.org/10.1158/1535-7163.MCT-05-0250
  32. Samarakoon, R., Overstreet, J. M. and Higgins, P. J. (2013) TGF-${\beta}$ signaling in tissue fibrosis: Redox controls, target genes and therapeutic opportunities. Cell. Signal. 25, 264-268. https://doi.org/10.1016/j.cellsig.2012.10.003
  33. Seiberg, M., Marthinuss, J. and Stenn, K. S. (1995) Changes in expression of apoptosis-associated genes in skin mark early catagen. J. Invest. Dermatol. 104, 78-82. https://doi.org/10.1111/1523-1747.ep12613555
  34. Senturk, S., Mumcuoglu, M., Gursoy-Yuzugullu, O., Cingoz, B., Akcali, K. C. and Ozturk, M. (2010) Transforming growth factor-${\beta}$ induces senescence in hepatocellular carcinoma cells and inhibits tumor growth. Hepatology 52, 966-974. https://doi.org/10.1002/hep.23769
  35. Silberstein, G. B. and Daniel, C. W. (1987) Reversible inhibition of mammary gland growth by transforming growth factor-${\beta}$. Science 237, 291-293. https://doi.org/10.1126/science.3474783
  36. Soma, T., Tsuji, Y. and Hibino, T. (2002) Involvement of transforming growth factor-${\beta}2$ in catagen induction during the human hair cycle. J. Invest. Dermatol. 118, 993-997. https://doi.org/10.1046/j.1523-1747.2002.01746.x
  37. Thannickal, V. J., Aldweib, K. D. and Fanburg, B. L. (1998) Tyrosine phosphorylation regulates $H_2O_2$ production in lung fibroblasts stimulated by transforming growth factor ${\beta}1$. J. Biol. Chem. 273, 23611-23615. https://doi.org/10.1074/jbc.273.36.23611
  38. Welker, P., Foitzik, K., Bulfone-Paus, S., Henz, B. M. and Paus, R. (1997) Hair cycle-dependent changes in the gene expression and protein content of transforming factor ${\beta}$ 1 and ${\beta}$ 3 in murine skin. Arch. Dermatol. Res. 289, 554-557. https://doi.org/10.1007/s004030050239
  39. Yan, F., Wang, Y., Wu, X., Peshavariya, H., Dusting, G., Zhang, M. and Jiang, F. (2014) Nox4 and redox signaling mediate TGF-${\beta}$-induced endothelial cell apoptosis and phenotypic switch. Cell Death Dis. 5, e1010. https://doi.org/10.1038/cddis.2013.551
  40. Yoon, Y. S., Lee, J. H., Hwang, S. C., Choi, K. S. and Yoon, G. (2005) TGF ${\beta}1$ induces prolonged mitochondrial ROS generation through decreased complex IV activity with senescent arrest in Mv1Lu cells. Oncogene 24, 1895-1903. https://doi.org/10.1038/sj.onc.1208262
  41. Zhang, Z., Chen, J., Jiang, X., Wang, J., Yan, X., Zheng, Y., Conklin, D. J., Kim, K. S., Kim, K. H., Tan, Y., Kim, Y. H. and Cai, L. (2014) The magnolia bioactive constituent 4-O-Methylhonokiol protects against high-fat diet-induced obesity and systemic insulin resistance in mice. Oxid. Med. Cell. Longev. 2014, 965954.

Cited by

  1. miR-770–5p inhibits the activation of pulmonary fibroblasts and silica-induced pulmonary fibrosis through targeting TGFBR1 vol.220, pp.None, 2017, https://doi.org/10.1016/j.ecoenv.2021.112372