Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Anti-tumorigenic Effects of Angelica gigase Nakai Extract on MBA-MB-231 through Regulating Lats1/2 Activation

유방암세포에서 LATS1/2 활성에 의한 당귀 추출물의 항암효과

  • Kim, Cho-Long (Department of Biomedical Sciences, Ajou University Graduate School of Medicine) ;
  • Kim, Nambin (Department of Biomedical Sciences, Ajou University Graduate School of Medicine) ;
  • Jeong, Han-Sol (Division of Applied Medicine, School of Korean Medicine, Pusan National University) ;
  • Shin, Yu-Su (Department of Ginseng and Medicinal Herb, National Institute of Horticultural and Herbal Science (NIHHS), Rural Development Administration (RDA)) ;
  • Mo, Jung-Soon (Institute of Medical Science, Ajou University School of Medicine)
  • Received : 2020.05.12
  • Accepted : 2020.07.23
  • Published : 2020.08.25
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Abstract

The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.

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References

  1. Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 2007;130(6):1120-33. https://doi.org/10.1016/j.cell.2007.07.019
  2. Pan D. The hippo signaling pathway in development and cancer. Developmental cell. 2010;19(4):491-505. https://doi.org/10.1016/j.devcel.2010.09.011
  3. Harvey KF, Zhang X, Thomas DM. The Hippo pathway and human cancer. Nature reviews Cancer. 2013;13(4):246-57. https://doi.org/10.1038/nrc3458
  4. Johnson R, Halder G. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nature reviews Drug discovery. 2014;13(1):63-79. https://doi.org/10.1038/nrd4161
  5. Mo JS, Park HW, Guan KL. The Hippo signaling pathway in stem cell biology and cancer. EMBO reports. 2014;15(6):642-56. https://doi.org/10.15252/embr.201438638
  6. Chan EH, Nousiainen M, Chalamalasetty RB, Schafer A, Nigg EA, Sillje HH. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene. 2005;24(12):2076-86. https://doi.org/10.1038/sj.onc.1208445
  7. Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW, Jaenisch R, et al. YAP1 increases organ size and expands undifferentiated progenitor cells. Current biology : CB. 2007;17(23):2054-60. https://doi.org/10.1016/j.cub.2007.10.039
  8. Hao Y, Chun A, Cheung K, Rashidi B, Yang X. Tumor suppressor LATS1 is a negative regulator of oncogene YAP. The Journal of biological chemistry. 2008;283(9):5496-509. https://doi.org/10.1074/jbc.M709037200
  9. Zhao B, Ye X, Yu J, Li L, Li W, Li S, et al. TEAD mediates YAP-dependent gene induction and growth control. Genes & development. 2008;22(14):1962-71. https://doi.org/10.1101/gad.1664408
  10. Yu FX, Guan KL. The Hippo pathway: regulators and regulations. Genes & development. 2013;27(4):355-71. https://doi.org/10.1101/gad.210773.112
  11. Piccolo S, Dupont S, Cordenonsi M. The biology of YAP/TAZ: hippo signaling and beyond. Physiological reviews. 2014;94(4):1287-312. https://doi.org/10.1152/physrev.00005.2014
  12. Hansen CG, Moroishi T, Guan KL. YAP and TAZ: a nexus for Hippo signaling and beyond. Trends in cell biology. 2015;25(9):499-513. https://doi.org/10.1016/j.tcb.2015.05.002
  13. Plouffe SW, Hong AW, Guan KL. Disease implications of the Hippo/YAP pathway. Trends in molecular medicine. 2015;21(4):212-22. https://doi.org/10.1016/j.molmed.2015.01.003
  14. Son SH, Park KK, Park SK, Kim YC, Kim YS, Lee SK, et al. Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine colon carcinoma. Phytotherapy research : PTR. 2011;25(7):959-64. https://doi.org/10.1002/ptr.3372
  15. Wan YQ, Liu YX, Guo L, Wan XF. [Determination of trace elements in danggui blood-supplementing decoction by ICP-AES]. Guang pu xue yu guang pu fen xi = Guang pu. 2007;27(1):160-4.
  16. Kim MR, Abd El-Aty AM, Choi JH, Lee KB, Shim JH. Identification of volatile components in Angelica species using supercritical-CO2 fluid extraction and solid phase microextraction coupled to gas chromatography-mass spectrometry. Biomedical chromatography : BMC. 2006;20(11):1267-73. https://doi.org/10.1002/bmc.696
  17. Kim MR, Abd El-Aty AM, Kim IS, Shim JH. Determination of volatile flavor components in danggui cultivars by solvent free injection and hydrodistillation followed by gas chromatographic-mass spectrometric analysis. Journal of chromatography A. 2006;1116(1-2):259-64. https://doi.org/10.1016/j.chroma.2006.03.060
  18. Heo BG, Chon SU, Park YJ, Bae JH, Park SM, Park YS, et al. Antiproliferative activity of Korean wild vegetables on different human tumor cell lines. Plant foods for human nutrition. 2009;64(4):257-63. https://doi.org/10.1007/s11130-009-0138-8
  19. Choi HS, Seo HS, Kim SR, Choi YK, Shin YC, Ko SG. Anti-inflammatory and anti-proliferative effect of herbal medicines (APR) in RAW264.7 cells. Molecular medicine reports. 2014;9(5):1569-74. https://doi.org/10.3892/mmr.2014.2033
  20. Jang JY, Kim J, Cai J, Kim Y, Shin K, Kim TS, et al. An ethanolic extract of Angelica gigas improves atherosclerosis by inhibiting vascular smooth muscle cell proliferation. Laboratory animal research. 2014;30(2):84-9. https://doi.org/10.5625/lar.2014.30.2.84
  21. Cho JH, Kwon JE, Cho Y, Kim I, Kang SC. Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression. Nutrients. 2015;7(6):4862-74. https://doi.org/10.3390/nu7064862
  22. Ku SK, Kim H, Kim JW, Kang KS, Lee HJ. Ameliorating effects of herbal formula hemomine on experimental subacute hemorrhagic anemia in rats. Journal of ethnopharmacology. 2017;198:205-13. https://doi.org/10.1016/j.jep.2017.01.010
  23. Kim JY, Yoon YD, Ahn JM, Kang JS, Park SK, Lee K, et al. Angelan isolated from Angelica gigas Nakai induces dendritic cell maturation through toll-like receptor 4. International immunopharmacology. 2007;7(1):78-87. https://doi.org/10.1016/j.intimp.2006.08.017
  24. Yim D, Singh RP, Agarwal C, Lee S, Chi H, Agarwal R. A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. Cancer research. 2005;65(3):1035-44.
  25. Mo JS, Meng Z, Kim YC, Park HW, Hansen CG, Kim S, et al. Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway. Nature cell biology. 2015;17(4):500-10. https://doi.org/10.1038/ncb3111
  26. Mo JS. The role of extracellular biophysical cues in modulating the Hippo-YAP pathway. BMB reports. 2017;50(2):71-8. https://doi.org/10.5483/BMBRep.2017.50.2.199
  27. Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, et al. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell. 2011;147(4):759-72. https://doi.org/10.1016/j.cell.2011.09.048
  28. Xin M, Kim Y, Sutherland LB, Murakami M, Qi X, McAnally J, et al. Hippo pathway effector Yap promotes cardiac regeneration. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(34):13839-44. https://doi.org/10.1073/pnas.1313192110
  29. Bartucci M, Dattilo R, Moriconi C, Pagliuca A, Mottolese M, Federici G, et al. TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells. Oncogene. 2015;34(6):681-90. https://doi.org/10.1038/onc.2014.5