DOI QR코드

DOI QR Code

Inhibitory Effect of Methanol Extract of Magnolia officinalis on Matrix Metalloproteinase-2

  • Lee, Dong-Yup (Department of Food Science and Technology, Kyungsung Universirty) ;
  • Kim, Cheorl-Ho (Department of Life Science, Sungkyunkwan University) ;
  • Kim, Dong-Soo (Department of Food Science and Technology, Kyungsung Universirty)
  • 발행 : 2006.09.01

초록

Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. The plant of Magnolia officinalis Rehd. et Wils. is often included as an ingredient in various herbal remedies recommended for cancer theraphies in Korea. Various extracts prepared from stems of M. officinalis were tested for cytotoxic activity on human hepatocellular carcinoma cell line, SK-Hep cells using the XTT assay method. Then, the inhibitory effect was examined on MMP-2 activity using gelatin zymography. Methanol (MeOH) extract of M. officinalis caused the strongest inhibition of the MMP-2 activity, as measured by gelatin zymography method for enzyme activity. $IC_{50}$ values of fractions on MMP-2 activity were in a range of $4.9{\sim}11.3\;{\mu}g/mL$. Among each fraction, butanol and ethylacetate (EtOAc) fractions showed the strong inhibitory activities ($IC_{50}=10.7\;and\;4.9\;{\mu}g/mL$, respectively). When the M. officinalis's constituents such as magnolol, honokiol, (-)-epigallocatechin gallate (EGCG) and ovovatol were examined for inhibitory effects on MMP-2 activity, EGCG showed strong inhibitory activity. However, MeOH extract of M. officinalis was dose-dependently inhibited to MMP-2 activity. The MeOH extract, hexane and EtOAc fractions $(IC_{50}\;of\;>200\;{\mu}g/mL)$ exhibited weak cytotoxicity activity, while butanol $(IC_{50}=80\;{\mu}g/mL)$ and chloroform fractions $(IC_{50}=90\;{\mu}g/mL)$ exhibited relatively strong cytotoxic activity. From these results, M. officinalis could be suitable for cancer treatment and chemopreventive drugs.

키워드

참고문헌

  1. Cawston TE. 1996. Matrix metalloproteinase inhibitors and the prevention of connective tissue breakdown. Pharmacol Ther 70: 163-182 https://doi.org/10.1016/0163-7258(96)00015-0
  2. Hiraoka NE, Allen IJ, Apel MR, Weiss SJ. 1998. Matrix metalloproteinases regulateneovascularization by acting as pericellular fibrinolysins. Cell 95: 365-377 https://doi.org/10.1016/S0092-8674(00)81768-7
  3. Liotta LA, Tryggvaason K, Garbisa S, Hart I, Foltz CM, Shafie S. 1980. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284: 67-68 https://doi.org/10.1038/284067a0
  4. Shima IY, Sasaguri J, Kusukawa H, Yamana H, Fujita T, Kakegawa, Morimatsu M. 1992. Production of matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal carcinoma. A clinicopathologic study. Cancer 70: 2747-2753 https://doi.org/10.1002/1097-0142(19921215)70:12<2747::AID-CNCR2820701204>3.0.CO;2-5
  5. Tokuraku MH, Sato S, Murakami Y, Okada Y, Seiki M. 1995. Activation of the precursor of gelatinase A/72 kDa type IV collagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT-MMP) and with lymph node metastasis. Int J Cancer 64: 355-359 https://doi.org/10.1002/ijc.2910640513
  6. Talyensaari-Mattila AP, Paakko M, Hoyhtya G, Turpeenniemi-Hujanen T. 1998. Matrix metalloproteinase-2 immunoreactive protein: a marker of aggressiveness in breast carcinoma. Cancer 83: 1153-1162 https://doi.org/10.1002/(SICI)1097-0142(19980915)83:6<1153::AID-CNCR14>3.0.CO;2-4
  7. Sier CF, Kubben KJ, Ganesh S, Heerding MM, Griffioen G, Hanemaaijer R, van Krieken JH, Lamers CB, Verspaget HW. 1996. Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma. Br J Cancer 74: 413-417 https://doi.org/10.1038/bjc.1996.374
  8. Whittaker MC, Floyd D, Brown P, Gearing AJH. 1999. Design and therapeutic application of matrix metalloproteinase inhibitors. Chem Rev 99: 2735-2776 https://doi.org/10.1021/cr9804543
  9. Bramhall SR, Rosemurgy A, Brown PD, Bowry C, Buckels JA. 2001. Marimastat Pancreatic Cancer Study Group, Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin  Oncol 19: 3447-3455 https://doi.org/10.1200/JCO.2001.19.15.3447
  10. Levitt NC, Eskens F, Propper DJ, Harris AL, Denis L, Ganesan TS, Mather RA, McKinley L, Planting A, Talbot DC, Van der Burg M, Wilner S, Verweij J. 1998. A phase one pharmacokinetic study of CGS 27023A, a matrix metalloproteinase inhibitor. Proc Am Soc Clin Oncol 17: 213-214
  11. Price A, Shi Q, Morris D, Wilcox ME, Brasher PMA, Rewcastle NB, Shalinsky D, Zou H, Applet K, Johnston RN, Yong VW, Edwards D, Forsyth P. 1999. Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340. Clin Cancer Res 5: 845-854
  12. Cha BY, Park CJ, Lee SG, Lee YC, Kim DW, Kim JD, Seo WG, Kim CH. 2003. Inhibitory effect of methanol extract of Euonymous alatus on matrix metalloproteinase-9. J Ethnopharm 85: 163-167 https://doi.org/10.1016/S0378-8741(02)00373-2
  13. Chang HM, But PH. 1986. Pharmacology and applications of Chinese materia medica. World Scientific Publishers, Singapore. Vol I, p 878-880
  14. Nagase H, Ikeda K, Sakai Y. 2001. Inhibitory effect of magnolol and honokiol from Magnolia obovata on human fibrosarcoma HT-1080 invasiveness in vitro. Planta Medica 67: 705-708 https://doi.org/10.1055/s-2001-18345
  15. Ikeda K, Nagase H. 2002. Magnolol has the ability to induce apoptosis in tumor cells. Biol Pharm Bull 25: 1546-1549 https://doi.org/10.1248/bpb.25.1546
  16. Yang SE, Hsieh MT, Tsai TH, Hsu SL. 2002. Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochem Pharmacol 63: 1641-1651 https://doi.org/10.1016/S0006-2952(02)00894-8
  17. Teng CM, Chen CC, Ko FN, Lee LG, Huang TF, Chen YP, Hsu HY. 1988. Two antiplatelet agents from Magnolia officinalis. Thromb Res 50: 757-765 https://doi.org/10.1016/0049-3848(88)90336-2
  18. Hirano T, Gotoh M, Oka K. 1994. Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Life Sci 55: 1061-1069 https://doi.org/10.1016/0024-3205(94)00641-5
  19. Kaegi E. 1998. Unconventional therapies for cancer: 2. Green tea. The task force on alternative therapies of the Canadian breast cancer research initiative. Canad Med Assoc J 158: 1033-1035
  20. Demeule M, Brossard M, Page M, Gingras D, Beliveau R. 2000. Matrix metalloproteinase inhibition by green tea catechins. Biochimica et Biophysica Acta 1478: 51-60 https://doi.org/10.1016/S0167-4838(00)00009-1
  21. Fujita MH, Itokawa, Sashida Y. 1973. Studies on the components of Magnolia obovata Thunb. II. On the components of the methanol extract of the bark. Yakugaku Zasshi 93: 422-428 https://doi.org/10.1248/yakushi1947.93.4_422
  22. Nebigil C, Malik KU. 1990. Prostaglandin synthesis elicited by adrenegic stimuli in rabbit aorta is mediated via alpha-1 and alpha-2 adrenergic receptors. J Pharmacol Exp Ther 254: 633-640
  23. Knight CG, Willenbrock F, Murphy G. 1992. A novel coumarin-labelled peptide for sensitive continuous assays of the matrix metalloproteinases. FEBS Lett 296: 263-266 https://doi.org/10.1016/0014-5793(92)80300-6
  24. Choi NS, Kim BY, Lee JY, Yoon KS, Han KY, Kim SH. 2002. Relationship between acrylamide concentration and enzymatic activity in an improved single fibrin zymogram gel system. J Biochem Mol Biol 35: 236-238 https://doi.org/10.5483/BMBRep.2002.35.2.236
  25. Aimes RT, Quigley JP. 1995. Matrix metalloproteinase-2 is an interstitial collagenase. J Biol Chem 270: 5872-5876 https://doi.org/10.1074/jbc.270.11.5872
  26. Woessner JF. 1991. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5: 2145-2154 https://doi.org/10.1096/fasebj.5.8.1850705
  27. Chung TW, Kim JR, Suh JI, Lee YC, Chang YC, Chung TH, Kim CH. 2004. Correlation between plasma levels of matrix metalloproteinase (MMP)-9/MMP-2 ratio and alpha-fetoproteins in chronic hepatitis carrying hepatitis B virus. J Gastroenterol Hepatol 19: 565-571 https://doi.org/10.1111/j.1440-1746.2004.03344.x
  28. Chung TW, Lee YC, Kim CH. 2004. Hepatitis B viral HBx induces matrix metalloproteinase-9 gene expression through activation of ERKs and PI-3K/AKT pathways: Involvement of invasive potential. FASEB J 18: 1123-1125 https://doi.org/10.1096/fj.03-1429fje
  29. Sato H, Takino T, Okada, Y, Cao J, Shinagawa A, Yamamoto E, Seiki M. 1994. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370: 61-65 https://doi.org/10.1038/370061a0
  30. Chung TW, Lee YC, Ko JH, Kim CH. 2003. Hepatitis B virus X protein (HBx) is a negative regulator of PTEN in liver cells: Involvement of AKT activation. Cancer Res 63: 3453-3458
  31. Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, Goldberg GI. 1995. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J Biol Chem 270: 5331-5338 https://doi.org/10.1074/jbc.270.10.5331
  32. Furumoto S, Iwata R, Ido T. 2002. Design and synthesis of fluorine-18 labeled matrix metalloproteinase inhibitors for cancer imaging. J Labelled Compd Radiopharm 45: 975-986 https://doi.org/10.1002/jlcr.616
  33. Furumoto S, Takashima K, Kubota K, Ido T, Iwata R, Fukuda H. 2003. Tumor detection using $^{(18)}F$-labeled matrix metalloproteinase-2 inhibitor. Nucl Med Biol 30: 119- 125 https://doi.org/10.1016/S0969-8051(02)00393-1