DOI QR코드

DOI QR Code

B16F10 흑색종 세포의 이동과 침윤에 미치는 동의보감 "유암" 처방에 근거한 한약복합처방들의 영향

Influence of Herb-combined Remedies Based on "Yooam" Prescription of Dongeuibogam on Migration and Invasion of B16F10 Melanoma Cells

  • 최은옥 (동의대학교 항노화연구소) ;
  • 권다혜 (동의대학교 항노화연구소) ;
  • 황보현 (동의대학교 항노화연구소) ;
  • 김민영 (동의대학교 항노화연구소) ;
  • 지선영 (동의대학교 항노화연구소) ;
  • 홍수현 (동의대학교 항노화연구소) ;
  • 박철 (동의대학교 자연과학대학 분자생물학과) ;
  • 황혜진 (동의대학교 의료.보건.생활대학 식품영양학과) ;
  • 최영현 (동의대학교 항노화연구소)
  • Choi, Eun Ok (Anti-Aging Research Center, Dong-eui University) ;
  • Kwon, Da Hye (Anti-Aging Research Center, Dong-eui University) ;
  • Hwang-Bo, Hyun (Anti-Aging Research Center, Dong-eui University) ;
  • Kim, Min Young (Anti-Aging Research Center, Dong-eui University) ;
  • Ji, Seon Yeong (Anti-Aging Research Center, Dong-eui University) ;
  • Hong, Su Hyun (Anti-Aging Research Center, Dong-eui University) ;
  • Park, Cheol (Department of Molecular Biology, College of Natural Sciences, Dong-eui University) ;
  • Hwang, Hye-Jin (Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dong-eui University) ;
  • Choi, Yung Hyun (Anti-Aging Research Center, Dong-eui University)
  • 투고 : 2018.07.29
  • 심사 : 2018.08.17
  • 발행 : 2018.08.31

초록

Objectives : We compared the inhibitory effects of herb-combined remedies, which were recorded on "Yooam" prescription of Dongeuibogam, on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, in B16F10 melanoma cells. For this purpose, water extracts of Sipyukmiryukieum (SYMRKU), Danjacheongpitang (DJCPT), Cheongganhaeultang (CGHUT) and Jipaesan (JPS) were used. Methods : Cytotoxicity was assessed by an MTT assay. Wound healing and matrigel transwell assays were used to examine on B16F10 cell migration and invasion. The levels of mRNA and protein expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were analyzed by RT-PCR and Western blotting. Results : Our data showed that DJCPT showed the strongest inhibitory effect among the four prescriptions in inhibiting cell motility of B16F10 melanoma cells within the concentration range that was not cytotoxic. The inhibitory potential of colony formation was higher in DJCPT and SYMRKU compared to the other two types of prescriptions, and the inhibitory effect of invasiveness is shown in order of DJCPT, SYMRKU, CGHUT and JPS. DJCPT, and SYMRKU strongly inhibited the activity and expression of MMP-2 and MMP-9, which are important mediators in cancer invasion, compared to CGHUT and JPS, and the increased expression of TIMP-1 and TIMP-2 was also more effective in these two prescriptions. In conclusion, DJCPT is expected to exhibit the most potent blocking effect on migration and invasion among four herb-combined remedies compared in B16F10 melanoma cells. Conclusion : Overall, the results of this study will be used as an important source to validate these prescriptions in animal models and to understand the mechanism of action of herbal remedies recorded in Dongeuibogam.

키워드

참고문헌

  1. Winer A, Adams S, Mignatti P. Matrix metalloproteinase inhibitors in cancer therapy: Turning past failures into future successes. Mol Cancer Ther. 2018;17:1147-55. https://doi.org/10.1158/1535-7163.MCT-17-0646
  2. Brown GT, Murray GI. Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 2015;237:273-81. https://doi.org/10.1002/path.4586
  3. Liu HY, Gu WJ, Wang CZ, Ji XJ, Mu YM. Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas: A systematic review and meta-analysis of case-control trials. Medicine (Baltimore). 2016;95:e3904. https://doi.org/10.1097/MD.0000000000003904
  4. Rudek MA, Venitz J, Figg WD. Matrix metalloproteinase inhibitors: do they have a place in anticancer therapy? Pharmacotherapy. 2002; 22:705-20. https://doi.org/10.1592/phco.22.9.705.34062
  5. Jablonska-Trypuc A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem. 2016; 31:177-83. https://doi.org/10.3109/14756366.2016.1161620
  6. Kessenbrock K, Wang CY, Werb Z. Matrix metalloproteinases in stem cell regulation and cancer. Matrix Biol. 2015;44-46:184-90. https://doi.org/10.1016/j.matbio.2015.01.022
  7. Shim SH, Kim JH, Choi JH, Jeong HW. Influences on the anticancer and inhibitive effects of the secondary effects by anticarcinogen of Shibyukmiyouki-Eum. J Orient Med Surg Ophthalmol Otolaryngol. 2002;15:302-14.
  8. Lee MH, Lee JW, Park C, Han MH, Hong SH, Choi YH. Antioxidant, antimicrobial and anticancer properties of seven traditional herb-combined remedies. J Life Sci. 2015; 25:406-15. https://doi.org/10.5352/JLS.2015.25.4.406
  9. Choi EO, Son DH, Kim MY, Hwang-Bo H, Kim HJ, Jeong JW, Hong SH, Park C, Choi YH. Antioxidant and antimicrobial activities of herb-combined remedies used in traditional Korean medicine for treating breast cancer. J Life Sci. 2016;26:680-8. https://doi.org/10.5352/JLS.2016.26.6.680
  10. Yi J, Kim B. Effects of Sipyukmiyukieum on DNA synthesis, cAMP synthesis and MHC-class II expression of FRTL-5 thyroid cells. Korean J Orient Int Med. 2005;26:398-408.
  11. Kim MY, Bo HH, Choi EO, Kwon DH, Kim HJ, Ahn KI, Ji SY, Jeong JW, Park SH, Hong SH, Kim GY, Park C, Kim HS, Moon SK, Yun SJ, Kim WJ, Choi YH. Induction of apoptosis by Citrus unshiu Peel in human breast cancer MCF-7 cells: Involvement of ROS-dependent activation of AMPK. Biol Pharm Bull. 2018; 41:713-21. https://doi.org/10.1248/bpb.b17-00898
  12. Kim MY, Choi EO, HwangBo H, Kwon DH, Ahn KI, Kim HJ, Ji SY, Hong SH, Jeong JW, Kim GY, Park C, Choi YH. Reactive oxygen species-dependent apoptosis induction by water extract of Citrus unshiu peel in MDA-MB-231 human breast carcinoma cells. Nutr Res Pract. 2018;12:129-34. https://doi.org/10.4162/nrp.2018.12.2.129
  13. Ahn KI, Choi EO, Kwon DH, HwangBo H, Kim MY, Kim HJ, Ji SY, Hong SH, Jeong JW, Park C, Kim ND, Kim WJ, Choi YH. Induction of apoptosis by ethanol extract of Citrus unshiu Markovich peel in human bladder cancer T24 cells through ROS-mediated inactivation of the PI3K/Akt pathway. Biosci Trends. 2017;11:565-73. https://doi.org/10.5582/bst.2017.01218
  14. Lee S, Ra J, Song JY, Gwak C, Kwon HJ, Yim SV, Hong SP, Kim J, Lee KH, Cho JJ, Park YS, Park CS, Ahn HJ. Extracts from Citrus unshiu promote immune-mediated inhibition of tumor growth in a murine renal cell carcinoma model. J Ethnopharmacol. 2011; 133:973-9. https://doi.org/10.1016/j.jep.2010.07.018
  15. Kim A, Im M, Gu MJ, Ma JY. Citrus unshiu peel extract alleviates cancer-induced weight loss in mice bearing CT-26 adenocarcinoma. Sci Rep. 2016;6:24214. https://doi.org/10.1038/srep24214
  16. Kang BH, Jung WS, Kim SB, Yoo SK. Effects of Chungganhaewooltang on serum levels of histamine and corticosterone and immune response after immobilization-stress or coldstress in mice. J Orient Obstet Gynecol. 2005;18:85-105.
  17. Lee SH, Park CK. Anti-inflammatory effects of Ji-Pae-San water extract. Korean J Orient Med Prescription. 2008;16:79-94.
  18. Hwang KM. Anti-leukemic effects of JIPAESAN and its components on leukemic cells HL-60. Korean J Orient Med Prescription 2002;10; 143-155.
  19. Heo SJ, Hwang DS, Lee JM, Lee CH, Lee KS, Jang JB. Antimetastatic effects of Jipae-san by inflammation control and activation of innate immune system. J Korean Obstet Gynecol. 2014; 27:1-14.
  20. Zhang Y, Chen Q. Relationship between matrix metalloproteinases and the occurrence and development of ovarian cancer. Braz J Med Biol Res. 2017;50:e6104.
  21. Chaudhary AK, Pandya S, Ghosh K, Nadkarni A. Matrix metalloproteinase and its drug targets therapy in solid and hematological malignancies: an overview. Mutat Res. 2013; 753:7-23. https://doi.org/10.1016/j.mrrev.2013.01.002
  22. Sampieri CL, Leon-Cordoba K, Remes-Troche JM. Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers. J Cancer Res Ther. 2013;9:356-63. https://doi.org/10.4103/0973-1482.119302
  23. Grzelczyk WL, Szemraj J, Jozefowicz-Korczynska M. The matrix metalloproteinase in larynx cancer. Postepy Hig Med Dosw (Online). 2016;70:1190-7.