생명과학회지 (Journal of Life Science)

  • 제19권1호
  • /
  • Pages.9-14
  • /
  • 2009
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

전호(Anthriscus sylvestris Hoffm)로부터 전립선 암세포 저해물질인 deoxypodophyllotoxin 의 탐색 및 분리

Screening and Purification of an Anti-Prostate Cancer Compound, Deoxypodophyllotoxin, from Anthriscus sylvestris Hoffm

  • 조효진 (부산대학교 의학전문대학원) ;
  • 유선녕 (부산대학교 의학전문대학원) ;
  • 김광연 (부산대학교 의학전문대학원) ;
  • 손재학 (신라대학교 의생명과학대학) ;
  • 오현철 (신라대학교 의생명과학대학) ;
  • 안순철 (부산대학교 의학전문대학원)
  • Cho, Hyo-Jin (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Yu, Sun-Nyoung (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Kim, Kwang-Youn (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Sohn, Jae-Hak (College of Medical and Life Sciences, Silla University) ;
  • Oh, Hyun-Cheol (College of Medical and Life Sciences, Silla University) ;
  • Ahn, Soon-Cheol (Department of Microbiology and Immunology, Pusan National University School of Medicine)
  • 발행 : 2009.01.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

전립선암은 현대 남성들에게 걸리기 쉬운 질병으로 나이가 들수록 발병의 위험이 증가하는 질환으로 현재 우리나라에서도 점점 증가하는 추세이다. 전립선암 치료법들은 치료영역이 제한적이고 재발할 가능성이 높아 근본적인 치료법으로는 사용되지는 못하므로 새로운 전립선암 치료 방법이 필요하다. 이에 본 연구에서는 100 여 가지의 한약재 methanol 추출물을 이용하여 MTT 방법으로 전립선암 세포주인 PC-3 세포에 대한 항증식 효과를 탐색하였으며 그 결과, A. sylvestris가 가장 강한 항증식 활성을 보였다. A. sylvestris의 methanol 추출물로부터 저해물질을 분리하기 위하여 100% methanol에서 2-3일 추출하고 난 뒤, ethyl acetate로 추출하고 silica gel, reverse phase-18, Sephadex LH-20 등의 컬럼 크로마토그래피를 이용하여 분리하였다. 최종적으로 활성분획을 HPLC로 분리하고 $4^{\circ}C$에서 methanal 용액에서 입방체 형태의 결정을 얻었으며 NMR 분광법과 이화학적 특성을 분석한 결과, deoxypodophyllotoxin 으로 동정되었다. 순수 분리된 deoxypodophyllotoxin은 전립선암의 세포주 PC-3 세포에서 처리 농도와 처리 시간 의존적인 항증식 효과를 보였다.

The prostate cancer is the critical health problem, increasing of its related death in worldwide. Unfortunately present surgery and chemotherapeutic choices seem to be impossible in curing or controlling prostate cancer, because metastasis occasionally advances even after these potentially curative therapies. Therefore, there is immediate need to alternative chemoprevention and chemotherapeutic agents. Over one hundred species of dried medicinal herbs were tested for proliferation inhibitory effects on prostate cancer cell line, PC-3. One of them, Anthriscus sylvestris was selected because of potent anti-proliferation effect. The dried root of A. sylvestris was extracted with 100% methanol for 2-3 days and its extract was fractionated by using ethyl acetate. And ethyl acetate layer was subjected to column chromatographies on silica gel, reverse phase-18 (RP-18) and Sephadex LH-20, in turn. Finally, the pure compound was obtained by crystallization in methanol at $4^{\circ}C$ for overnight and identified as deoxypodophyllotoxin by NMR spedorscopic and physico-chemical analyses. In addition, it was confirmed that deoxypodophyllotoxin clearly inhibits the proliferation of PC-3 cells in a dose and time-dependent manner.

키워드

참고문헌

  1. Abdulla, M. and P. Gruber. 2000. Role of diet modification in cancer prevention. Biofactors 12, 45-5 https://doi.org/10.1002/biof.5520120108
  2. Arunkumar, A., M. R. Vijayababu, N. Srinivasan, M. M. Aruldhas and J. Arunakaran, 2006. Garlic compound, diallyl disulfide induces cell cycle arrest in prostate cancer cell line PC-3. Mol. Cell Biochem. 288, 107-113
  3. Denmeade, S. R., X. S. Lin and J. T. Isaacs. 1996. Role of programmed (apoptotic) cell death during the progression and therapy for prostate cancer. Prostate 28, 251-265 https://doi.org/10.1002/(SICI)1097-0045(199604)28:4<251::AID-PROS6>3.0.CO;2-G
  4. Fleischer, A., A. Ghadiri, F. Dessauge, M. Duhamel, M. P. Rebollo, F. Alvarez-Franco and A. Rebollo. 2006. Modulating apoptosis as a target for effective therapy. Mol. Immunol. 43, 1065-1079 https://doi.org/10.1016/j.molimm.2005.07.013
  5. Furre, I. E., M. T. Moller, S. Shahzidi, J. M. Nesland and Q. Peng. 2006. Involvement of both caspase-dependent and -independent pathways in apoptotic induction by hexaminolevulinate-mediated photodynamic therapy in human lymphoma cells. Apoptosis 11, 2031-2042 https://doi.org/10.1007/s10495-006-0190-x
  6. Gilligan, T. and P. W. Kantoff. 2002. Chemotherapy for prostate cancer. Urology 60, S94-S100 https://doi.org/10.1016/S0090-4295(02)01583-2
  7. Gordaliza, M., J. M. Miguel del Corral, M. Angeles Castro, P. A. García-García and A. San Feliciano. 2001. Cytotoxic cyclolignans related to podophyllotoxin. Farmaco. 56, 297-304 https://doi.org/10.1016/S0014-827X(01)01030-8
  8. Jemal, A., T. Murray, E. Ward, A. Samuels, R. C. Tiwari, A. Ghafoor, E. J. Feuer and M. J. Thun. 2005. Cancer statistics. 2005. CA Cancer J. Clin. 55, 10-30 https://doi.org/10.3322/canjclin.55.1.10
  9. Jeong, G. S., O. K. Kwon, B. Y. Park, S. R. Oh, K. S. Ahn, M. J. Chang, W. K Oh, J. C. Kim, B. S. Min, Y. C. Kim and H. K. Lee. 2007. Lignans and coumarins from the roots of Anthriscus sylvestris and their increase of caspase-3 activity in HL-60 cells. Biol. Pharm. Bull. 30, 1340-1343 https://doi.org/10.1248/bpb.30.1340
  10. Ko, S. H., S. H. Do, Y. S. Kwon and C. M. Kim. 1992. A Study on the chemical components from the roots of Anthriscus sylvestris. Kor. J. Pharmacogn. 23, 225-228
  11. Krishnan, K., S. Campbell, F. Abdel-Rahman, S. Whaley and W. T. Stone. 2003. Cancer chemoprevention drug targets. Curr. Drug Targets 4, 45-54 https://doi.org/10.2174/1389450033347028
  12. Kutuk, O. and H. Basaga. 2006. Bcl-2 protein family: implications in vascular apoptosis and atherosclerosis. Apoptosis 11, 1661-1675 https://doi.org/10.1007/s10495-006-9402-7
  13. Laufer, M., S. R. Denmeade, V. J. Sinibaldi, M. A. Carducci and M. A. Eisenberger. 2000. Complete androgen blockade for prostate cancer：what went wrong? J. Urol. 164, 3-9 https://doi.org/10.1016/S0022-5347(05)67436-8
  14. Lowe, S. W. and A. W. Lin. 2000. Apoptosis in cancer. Carcinogenesis 21, 485-495 https://doi.org/10.1093/carcin/21.3.485
  15. Mann, J. 2002. Natural products in cancer chemotherapy: past, present and future. Nat. Rev. Cancer 2, 143-148 https://doi.org/10.1038/nrc723
  16. Mantena, S. K., S. D. Sharma and S. K. Katiyar. 2006. Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol. Cancer Ther. 5, 296-308 https://doi.org/10.1158/1535-7163.MCT-05-0448
  17. Reddy, L., B. Odhav and K. D. Bhoola. 2003. Natural products for cancer prevention: a global perspective. Pharmacol. Ther. 99, 1-13 https://doi.org/10.1016/S0163-7258(03)00042-1
  18. Swanson, G. P., M. Riggs and J. Earle. 2004. Failure after primary radiation or surgery for prostate cancer; differences in response to androgen ablation. J. Urol. 172, 525-528 https://doi.org/10.1097/01.ju.0000132412.74468.57
  19. Swanson, G. P. 2006. Management of locally advanced prostate cancer; past, present, future. J. Urol. 176, S34-S41 https://doi.org/10.1016/j.juro.2006.06.079
  20. Thurman, S. A., N. R. Ramakrishna and T. L. DeWeese. 2001. Radiation therapy for the treatment of locally advanced and metastatic prostate cancer. Hematol. Oncol. Clin. North Am. 15, 423-443 https://doi.org/10.1016/S0889-8588(05)70224-0
  21. Wang, G., H. Chen, M. Huang, N. Wang, J. Zhang, Y. Zhang, G. Bai, W. F. Fong, M. Yang and X. Yao. 2006. Methyl protodioscin induces G2/M cell cycle arrest and apoptosis in HepG2 liver cancer cells. Cancer Lett. 241, 102-109 https://doi.org/10.1016/j.canlet.2005.10.050

피인용 문헌

  1. Deoxypodophyllotoxin induces cytoprotective autophagy against apoptosis via inhibition of PI3K/AKT/mTOR pathway in osteosarcoma U2OS cells vol.69, pp.5, 2017, https://doi.org/10.1016/j.pharep.2017.04.007
  2. Interplay of reactive oxygen species, intracellular Ca2+and mitochondrial homeostasis in the apoptosis of prostate cancer cells by deoxypodophyllotoxin vol.114, pp.5, 2013, https://doi.org/10.1002/jcb.24455