Antineoplastic Effect of Several Herbal Medicines on SNU-80 Anaplastic Thyroid Carcinoma Cell Line

황기, 당귀, 칠피, 천화분의 역형성갑상선암세포 SNU-80에 대한 항암효과

  • Yeo, Hyun Soo (Department of Korean Internal Medicine, College of Korean Medicine, Gachon University) ;
  • Lee, Min Hye (Department of Korean Internal Medicine, College of Korean Medicine, Gachon University) ;
  • Ko, Seong Gyu (Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Choi, You Kyung (Department of Korean Internal Medicine, College of Korean Medicine, Gachon University) ;
  • Jun, Chan Young (Department of Korean Internal Medicine, College of Korean Medicine, Gachon University) ;
  • Park, Jong Hyeong (Department of Korean Internal Medicine, College of Korean Medicine, Gachon University)
  • 여현수 (가천대학교 한의과대학 내과학교실) ;
  • 이민혜 (가천대학교 한의과대학 내과학교실) ;
  • 고성규 (경희대학교 한의과대학 예방의학교실) ;
  • 최유경 (가천대학교 한의과대학 내과학교실) ;
  • 전찬용 (가천대학교 한의과대학 내과학교실) ;
  • 박종형 (가천대학교 한의과대학 내과학교실)
  • Received : 2014.03.31
  • Accepted : 2014.04.12
  • Published : 2014.04.30

Abstract

Objective : This study was performed to investigate the antineoplastic effect of Astragalus membranaceus, Angelica gigas, Rhus verniciflua Stokes and Trichosanthes kirilowii on SNU-80 anaplastic thyroid carcinoma cell line. Method : We examined whether our herbal medicines decreases cell growth rate of SNU-80 using MTT assay. We performed western blot analysis to verify that our herbal medicines induces apoptosis via caspase-dependent mechanism. We also performed wound healing assay and transwell invasion assay to investigate whether our herbal medicines affects the migration and invasion of anaplastic cancer cells, SNU-80. We also carried out ELISA assay to know our herbal medicines suppresses the expression of proinvasive molecules, such as VEGF and MMP-2 secreted from SNU-80. Results : MTT assay demonstrates that Angelica gigas, Rhus verniciflua Stokes, and Trichosanthes kirilowii suppressed strongly the growth of SNU-80. Western blot analysis demonstrates that Trichosanthes kirilowii induces apoptosis activating the cleavages of caspases (caspase-8, caspase-3) and PARP. Wound healing assay demonstrates that Rhus verniciflua Stokes, and Trichosanthes kirilowii inhibited the migration of SNU-80. Transwell invasion assay demonstrates that Rhus verniciflua Stokes, and Trichosanthes kirilowii inhibited the invasion of SNU-80. Elisa assay demonstrates that Astragalus membranaceus, Angelica gigas, Rhus verniciflua Stokes, and Trichosanthes kirilowii suppressed the expression of VEGF and MMP-2. Conclusion : We could conclude that several herbal medicines suppresses the growth and inhibits the migration and invasion of SNU-80 which is anaplastic thyroid cancer cells. Especially, Rhus verniciflua Stokes, Trichosanthes kirilowii had stronger anti-cancer effect suggesting that we can apply them to treat anaplastic thyroid cancer.

Keywords

References

  1. 대한내과학회. 해리슨내과학 제17판. 서울:도서출판 MIP. 2010;2699, 2703.
  2. 대한병리학회. 병리학 제6판. 서울:KMS. 2007;904,
  3. Pasieka JL. Anaplastic Thyroid Cancer. Curr Opin Oncol. 2003;15:78-83. https://doi.org/10.1097/00001622-200301000-00012
  4. Kim TY, Kim KW, Jung TS, Kim JM, Kim SW, Chung KW, Kim EY, Gong G, Oh YL, Cho SY, Yi KH, Kim WB, Park Do J, Chung JH, Cho BY, Shong TK. Prognostic Factors for Korean Patients with Anaplastic Thyroid Carcinoma. Head Neck. 2007;29:765-72. https://doi.org/10.1002/hed.20578
  5. 최현정, 김태용, 김의용, 김원구, 김원배, 송영기. 심바스타틴이 미분화 갑상선암 세포주의 성장 및 침습에 미치는 영향. 대한내분비학회지. 2008;23 (4):238-44.
  6. 류기원, 전병욱, 류봉하, 박동원. 암에 대한 한의학적 인식 및 실험적 연구에 관한 고찰. 대한한방종양학회지. 1995;1(1):29-54.
  7. 崔昇勳. 東醫腫瘍學. 서울:杏林書院. 1995;13-42.
  8. 전통의학연구소. 한의학사전. 서울:成輔社. 2001;233.
  9. 정재중, 구선영, 임새롬, 성정석, 김동일. 四物湯加 味方의 항암효과에 대한 실험적 연구. 대한한방부인과학회지. 2010;23(3):38-55.
  10. 전국한의과대학 본초학공동교재 편집위원회. 本草學. 서울:永林社. 2012; 205, 477, 573, 577, 630.
  11. 주영증, 정종길. 약용자원식물학. 서울:永林社. 2005; 207, 239, 247.
  12. 中藥大辭典 編纂委員會. 中藥大辭典. 서울:정담. 1997; 4374.
  13. 이현희, 임은미. 자궁경부암세포에 대한 天花粉의 성장억제 및 세포사멸효과. 대한한방부인과학회지. 2005;18(3):77-91.
  14. 최태연, 이성원, 류연희, 반효정, 서근영, 김재효, 안성훈, 손인철. 천화분 약침액의 A549 폐암세포 주에서 apoptosis 유발효과. 경락경혈학회지. 2010; 27(4):15-23.
  15. 최원철, 이재호, 이은옥, 이효정, 윤성우, 안규석, 김성훈. 법제 옻나무 추출물의 혈관형성저해 및 항 암효과에 대한 연구. 대한암한의학회지. 2006;11(1): 23-30.
  16. 의학교육연수원. 가정의학. 서울:서울대학교출판부. 2003;470-1, 475.
  17. Yawara Yoshitoshi. 內科診斷學 改訂6版. 서울: 제일의학사. 1994;538.
  18. 許浚. 東醫寶鑑. 서울:여강출판사. 2001;2253.
  19. 傳統文化硏究所. 東洋醫學大辭典. 서울:成輔社 2000; 467, 1080.
  20. 김성동. 白花蛇舌草로부터 분리한 ursolic acid의 자연살해효과와 항전이작용. 대전대학교한의학연구소논문집. 1997;5(2):523-33.
  21. 송호준, 김대현. 白花蛇舌草 전탕액 투여가 마우스 의 항종양 면역반응에 미치는 영향. 본초분과학회지. 1994;9(1):3-97.
  22. 邢雪梅. 抗癌中藥의 生物治療效能硏究近況. 한글판 中醫雜誌. 1994;85-90.
  23. 이영찬, 전병훈. 파두를 가미한 사군자탕 및 사물탕의 항암효과에 대한 연구. 동의병리생리학회지. 1994;9(1):79-100.
  24. Wlodkowic D, Skommer J, Darzynkiewicz Z. Cytometry of apoptosis. Historical perspective and new advances. Exp Oncol. 2012;34(3): 255-62.
  25. Liwak U, Faye MD, Holcik M. Translation control in apoptosis. Exp Oncol. 2012;34(3): 218-30.
  26. Weerasinghe P, Buja LM. Oncosis: An important non-apoptotic mode of cell death. Exp Mol Pathol. 2012.
  27. Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, Bao JK. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 2012;45(6):487-98. https://doi.org/10.1111/j.1365-2184.2012.00845.x
  28. Perrin AJ, Gunda M, Yu B, Yen K, Ito S, Forster S, Tissenbaum HA, Derry WB. Noncanonical control of C. elegans germline apoptosis by the insulin/IGF-1 and Ras/MAPK signaling pathways. Cell Death Differ. 2012.
  29. Bhujade A, Gupta G, Talmale S, Das SK, Patil MB. Induction of apoptosis in A431 skin cancer cells by Cissus quadrangularis Linn stem extract by altering Bax-Bcl-2 ratio, release of cytochrome c from mitochondria and PARP cleavage. Food Funct. 2012.
  30. Weyhenmeyer B, Murphy AC, Prehn JH, Murphy BM. Targeting the anti-apoptotic bcl-2 family members for the treatment of cancer. Exp Oncol. 2012;34(3):192-9.
  31. Monian P, Jiang X. Clearing the final hurdles to mitochondrial apoptosis: regulation post cytochrome C release. Exp Oncol. 2012;34(3): 185-91.
  32. Fiandalo MV, Kyprianou N. Caspase control: protagonists of cancer cell apoptosis. Exp Oncol. 2012;34(3):165-75.
  33. Rodriguez LG, Wu X, Guan JL. Wound-healing assay. Methods Mol Biol. 2005;294:23-9.
  34. Marshall J. Transwell((R)) invasion assays. Methods Mol Biol. 2011;769:97-110. https://doi.org/10.1007/978-1-61779-207-6_8
  35. Sharma C, Nusri Qel-A, Begum S, Javed E, Rizvi TA, Hussain A. (-)-epigallocatechin- 3-gallate induces apoptosis and inhibits invasion and migration of human cervical cancer cells. Asian Pac J Cancer Prev. 2012;13(9):4815-22. https://doi.org/10.7314/APJCP.2012.13.9.4815
  36. Wang L, Wang X, Liang Y, Diao X, Chen Q. S100A4 promotes invasion and angiogenesis in breast cancer MDA-MB-231 cells by upregulating matrix metalloproteinase-13. Acta Biochim Pol. 2012.
  37. Gao W, Sweeney C, Walsh C, Rooney P, Mc- Cormick J, Veale DJ, Fearon U.Notch signalling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2. Ann Rheum Dis. 2012.
  38. Aricò A, Giantin M, Gelain M, Riondato F, Mortarino M, Comazzi S, Dacasto M, Castagnaro M, Aresu L. Matrix metalloproteinases and vascular endothelial growth factor expression in canine leukaemias. Vet J. 2012.
  39. Yarani R, Mansouri K, Mohammadi-Motlagh HR, Mahnam A, Emami Aleagha MS. In vitro inhibition of angiogenesis by hydroalcoholic extract of oak (Quercus infectoria) acorn shell via suppressing VEGF, MMP-2, and MMP-9 secretion. Pharm Biol. 2012
  40. Siejka A, Barabutis N, Schally AV. GHRH antagonist inhibits focal adhesion kinase (FAK) and decreases expression of vascular endothelial growth factor (VEGF) in human lung cancer cells in vitro. Peptides. 2012;37(1):63-8. https://doi.org/10.1016/j.peptides.2012.07.010
  41. Li X, Ji Z, Ma Y, Qiu X, Fan Q, Ma B. Expression of hypoxia-inducible factor-$1\alpha$, vascular endothelial growth factor and matrix metalloproteinase-2 in sacral chordomas. Oncol Lett. 2012;3(6):1268-74.
  42. Peter Hornbeck, Scott E. Winston, Steven A. Fuller. Enzyme‐Linked Immunosorbent Assays (ELISA). Current protocols. 2001.