DOI QR코드

DOI QR Code

Ginsenoside F1 Modulates Cellular Responses of Skin Melanoma Cells

  • Yoo, Dae-Sung (College of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University) ;
  • Rho, Ho-Sik (R&D Center, Amore-Pacific Co.) ;
  • Lee, Yong-Gyu (College of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University) ;
  • Yeom, Myung-Hun (R&D Center, Amore-Pacific Co.) ;
  • Kim, Duck-Hee (R&D Center, Amore-Pacific Co.) ;
  • Lee, Sang-Jin (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Hong, Sung-Youl (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Lee, Jae-Hwi (College of Pharmacy, Chung-Ang University) ;
  • Cho, Jae-Youl (Department of Genetic Engineering, Sungkyunkwan University)
  • Received : 2010.11.01
  • Accepted : 2010.11.10
  • Published : 2011.03.29

Abstract

Ginsenoside (G)-F1 is an enzymatic metabolite generated from G-Rg1. Although this metabolite has been reported to suppress platelet aggregation and to reduce gap junction-mediated intercellular communication, the modulatory activity of G-F1 on the functional role of skin-derived cells has not yet been elucidated. In this study, we evaluated the regulatory role of G-F1 on the cellular responses of B16 melanoma cells. G-F1 strongly suppressed the proliferation of B16 cells up to 60% at 200 ${\mu}g/mL$, while only diminishing the viability of HEK293 cells up to 30%. Furthermore, G-F1 remarkably induced morphological change and clustering of B16 melanoma cells. The melanin production of B16 cells was also significantly blocked by G-F1 up to 70%. Interestingly, intracellular signaling events involved in cell proliferation, migration, and morphological change were up-regulated at 1 h incubation but down-regulated at 12 h. Therefore, our results suggest that G-F1 can be applied as a novel anti-skin cancer drug with anti-proliferative and anti-migration features.

Keywords

References

  1. Meyskens FL Jr, Farmer P, Fruehauf JP. Redox regulation in human melanocytes and melanoma. Pigment Cell Res 2001;14:148-154. https://doi.org/10.1034/j.1600-0749.2001.140303.x
  2. Wood JM, Gibbons NC, Schallreuter KU. Melanocortins in human melanocytes. Cell Mol Biol (Noisy-le-grand) 2006;52:75-78.
  3. Slominski A, Wortsman J, Carlson AJ, Matsuoka LY, Balch CM, Mihm MC. Malignant melanoma. Arch Pathol Lab Med 2001;125:1295-1306.
  4. Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol 2009;15:3073-3085. https://doi.org/10.3748/wjg.15.3073
  5. Hasegawa H. Proof of the mysterious effi cacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. J Pharmacol Sci 2004;95:153-157. https://doi.org/10.1254/jphs.FMJ04001X4
  6. Wakabayashi C, Murakami K, Hasegawa H, Murata J, Saiki I. An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun 1998;246:725-730. https://doi.org/10.1006/bbrc.1998.8690
  7. Choo MK, Sakurai H, Kim DH, Saiki I. A ginseng saponin metabolite suppresses tumor necrosis factor-alpha-promoted metastasis by suppressing nuclear factor-kappaB signaling in murine colon cancer cells. Oncol Rep 2008;19:595-600.
  8. Ko SR, Choi KJ, Uchida K, Suzuki Y. Enzymatic preparation of ginsenosides Rg2, Rh1, and F1 from protopanaxatriol-type ginseng saponin mixture. Planta Med 2003;69:285-286. https://doi.org/10.1055/s-2003-38476
  9. Wang J, Huang ZG, Cao H, Wang YT, Hui P, Hoo C, Li SP. Screening of anti-platelet aggregation agents from Panax notoginseng using human platelet extraction and HPLCDAD-ESI-MS/MS. J Sep Sci 2008;31:1173-1180. https://doi.org/10.1002/jssc.200700507
  10. Zhang YW, Dou DQ, Zhang L, Chen YJ, Yao XS. Effects of ginsenosides from Panax ginseng on cell-to-cell communication function mediated by gap junctions. Planta Med 2001;67:417-422. https://doi.org/10.1055/s-2001-15816
  11. Shin YW, Bae EA, Kim SS, Lee YC, Kim DH. Effect of ginsenoside Rb1 and compound K in chronic oxazoloneinduced mouse dermatitis. Int Immunopharmacol 2005;5:1183-1191. https://doi.org/10.1016/j.intimp.2005.02.016
  12. Shin YW, Bae EA, Kim DH. Inhibitory effect of ginsenoside Rg5 and its metabolite ginsenoside Rh3 in an oxazolone-induced mouse chronic dermatitis model. Arch Pharm Res 2006;29:685-690.
  13. Cho JY, Fox DA, Horejsi V, Sagawa K, Skubitz KM, Katz DR, Chain B. The functional interactions between CD98, beta1-integrins, and CD147 in the induction of U937 homotypic aggregation. Blood 2001;98:374-382. https://doi.org/10.1182/blood.V98.2.374
  14. Lee YW, Kim PH, Lee WH, Hirani AA. Interleukin-4, oxidative stress, vascular infl ammation and atherosclerosis. Biomol Ther 2010;18:135-144. https://doi.org/10.4062/biomolther.2010.18.2.135
  15. Lee JY, Lee YG, Lee J, Yang KJ, Kim AR, Kim JY, Won MH, Park J, Yoo BC, Kim S, et al. Akt Cys-310-targeted inhibition by hydroxylated benzene derivatives is tightly linked to their immunosuppressive effects. J Biol Chem 2010;285:9932-9948. https://doi.org/10.1074/jbc.M109.074872
  16. Shim JH, Choi CS, Lee EC, Kim MY, Chun YJ. Tamoxifen suppresses clusterin level through Akt inactivation and proteasome degradation in human prostate cancer cells. Biomol Ther 2009;17:25-31. https://doi.org/10.4062/biomolther.2009.17.1.25
  17. Lee EH, Cho SY, Kim SJ, Shin ES, Chang HK, Kim DH, Yeom MH, Woe KS, Lee J, Sim YC, et al. Ginsenoside F1 protects human HaCaT keratinocytes from ultraviolet-B-induced apoptosis by maintaining constant levels of Bcl-2. J Invest Dermatol 2003;121:607-613. https://doi.org/10.1046/j.1523-1747.2003.12425.x
  18. Niederman R, Amrein PC, Hartwig J. Three-dimensional structure of actin filaments and of an actin gel made with actin-binding protein. J Cell Biol 1983;96:1400-1413. https://doi.org/10.1083/jcb.96.5.1400
  19. Cho JY, Katz DR, Chain BM. Staurosporine induces rapid homotypic intercellular adhesion of U937 cells via multiple kinase activation. Br J Pharmacol 2003;140:269-276. https://doi.org/10.1038/sj.bjp.0705436
  20. Cho JY, Chain BM, Vives J, Horejsi V, Katz DR. Regulation of CD43-induced U937 homotypic aggregation. Exp Cell Res 2003;290:155-167. https://doi.org/10.1016/S0014-4827(03)00322-7
  21. Park HY, Kosmadaki M, Yaar M, Gilchrest BA. Cellular mechanisms regulating human melanogenesis. Cell Mol Life Sci 2009;66:1493-1506. https://doi.org/10.1007/s00018-009-8703-8
  22. Virador VM, Kobayashi N, Matsunaga J, Hearing VJ. A standardized protocol for assessing regulators of pigmentation. Anal Biochem 1999;270:207-219. https://doi.org/10.1006/abio.1999.4090
  23. Lee YG, Lee WM, Kim JY, Lee JY, Lee IK, Yun BS, Rhee MH, Cho JY. Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells. Br J Pharmacol 2008;154:852-863.
  24. Cho JY, Kim AR, Joo HG, Kim BH, Rhee MH, Yoo ES, Katz DR, Chain BM, Jung JH. Cynaropicrin, a sesquiterpene lactone, as a new strong regulator of CD29 and CD98 functions. Biochem Biophys Res Commun 2004;313:954-961. https://doi.org/10.1016/j.bbrc.2003.12.026

Cited by

  1. Bone Marrow Cells in Porcine vol.16, pp.3, 2012, https://doi.org/10.4196/kjpp.2012.16.3.167
  2. Co-transformation of Panax major ginsenosides Rb1 and Rg1 to minor ginsenosides C–K and F1 by Cladosporium cladosporioides vol.39, pp.4, 2012, https://doi.org/10.1007/s10295-011-1058-9
  3. HangAmDan-B, an Ethnomedicinal Herbal Mixture, Suppresses Inflammatory Responses by Inhibiting Syk/NF-κB and JNK/ATF-2 Pathways vol.16, pp.1, 2013, https://doi.org/10.1089/jmf.2012.2374
  4. T-cell-derived interleukin 13 in the skin-whitening effect of Ginsenoside F1 vol.23, pp.11, 2014, https://doi.org/10.1111/exd.12531
  5. Natural products as photoprotection vol.14, pp.1, 2015, https://doi.org/10.1111/jocd.12123
  6. Recent advances in ginseng as cancer therapeutics: a functional and mechanistic overview vol.32, pp.2, 2015, https://doi.org/10.1039/C4NP00080C
  7. berry mediated gold nanoparticles as safe and efficient novel cosmetic material pp.2169-141X, 2018, https://doi.org/10.1080/21691401.2017.1307216
  8. Synthesis of a Novel α-Glucosyl Ginsenoside F1 by Cyclodextrin Glucanotransferase and Its In Vitro Cosmetic Applications vol.8, pp.4, 2018, https://doi.org/10.3390/biom8040142
  9. Src and Syk are targeted to an anti-inflammatory ethanol extract of Aralia continentalis vol.143, pp.2, 2011, https://doi.org/10.1016/j.jep.2012.07.031
  10. Protective Effect of Processed Panax ginseng, Sun Ginseng on UVB-irradiated Human Skin Keratinocyte and Human Dermal Fibroblast vol.36, pp.1, 2011, https://doi.org/10.5142/jgr.2012.36.1.68
  11. Ginsenoside F1 attenuates hyperpigmentation in B16F10 melanoma cells by inducing dendrite retraction and activating Rho signalling vol.24, pp.2, 2011, https://doi.org/10.1111/exd.12586
  12. Ginseng-berry-mediated gold and silver nanoparticle synthesis and evaluation of their in vitro antioxidant, antimicrobial, and cytotoxicity effects on human dermal fibroblast and murine melanoma skin vol.12, pp.None, 2017, https://doi.org/10.2147/ijn.s118373
  13. Gram-Scale Production of Ginsenoside F1 Using a Recombinant Bacterial β-Glucosidase vol.27, pp.9, 2011, https://doi.org/10.4014/jmb.1703.03006
  14. Synthesis of 20S-Protopanaxatriol β-D-Glucopyranosides vol.55, pp.1, 2011, https://doi.org/10.1007/s10600-019-02618-6