한국식품영양학회지 (The Korean Journal of Food And Nutrition)

  • 제25권4호
  • /
  • Pages.713-718
  • /
  • 2012
  • /
  • 1225-4339(pISSN)
  • /
  • 2287-4992(eISSN)
한국식품영양학회 (The Korean Society of Food and Nutrition)
권호 표지
DOI QR코드

DOI QR Code

향나무 추출물의 Galectin-3 저해에 의한 암 전이 억제 효과

Anti-Metastatic Activity of Juniperus chinensis Extract by Galectin-3 Inhibition

  • Lee, Keyong Ho (Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc.) ;
  • Rhee, Ki-Hyeong (College of Industrial Sciences, Kongju National University)
  • 투고 : 2012.08.22
  • 심사 : 2012.10.05
  • 발행 : 2012.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

향나무 에탄올 추출물에 대한 암 전이 억제 효과를 측정하기 위하여 세포 수준에서 암 전이에 밀접히 관련되어 있는 galectin-3에 대한 억제 효과를 colon 26-M3.1 lung carcinoma에서 측정하였다. 향나무 추출물 $5{\mu}g/m{\ell}$, $50{\mu}g/m{\ell}$ 및 $500{\mu}g/m{\ell}$ 처리 시, 농도 의존적으로 galectin-3에 대한 저해 효과를 나타내었다. 한편, 암 전이 관련 있는 또 다른 단백질로 MMP 효소에 대한 직접적인 억제효과를 측정한 결과, 향나무 추출물 $5{\mu}g/m{\ell}$, $50{\mu}g/m{\ell}$ 및 $500{\mu}g/m{\ell}$ 처리 시 직접적으로 MMP-1, MMP-2 및 MMP-9 효소에 대해서 농도의존적인 저해 효과는 나타났으나, 강한 활성으로 평가되지는 못하였다. Colon 26-M3.1 lung carcinoma을 이용한 in vivo mouse 모델에서 향나무 추출은 농도 의존적으로 전이 억제 효과를 나타내었고, MMP-2 활성화 물질인 relaxin과 병용투여 시, relaxin의 기능에 영향을 받지 않는 것으로 나타났다. 따라서 in vivo mouse 모델에서 나타난 암 전이 억제 효과는 galectin-3 저해로 인한 효과로 사료된다.

The purpose of this study was to examine the anti-metastatic effect of Juniperus chinensis extract by inhibition of galectin-3 expression. For this study, we carried out the experiment of galectin-3 expression assay and in vivo metastasis mouse model bearing colon 26-M3.1 lung carcinoma, and also MMP-1, MMP-2 and MMP-9 inhibitory assays relating metastasis mechanism. J. chinensis extract significantly showed the inhibitory effect of basal expression and MNNG-induced expression of galectin-3 in colon 26-M3.1 lung carcinoma at the all tested doses (5, 50 and $500{\mu}g/m{\ell}$). In case of the inhibition of MMP-1, MMP-2 and MMP-9, the weak activity was showed at the doses of 50 and $500{\mu}g/m{\ell}$ and was not detected at the dose of $5{\mu}g/m{\ell}$. However, J. chinensis extract significantly showed the anti-metastatic activity on mouse mode bearing colon 26-M3.1 lung carcinoma. Therefore, this study strongly suggests that J. chinensis is a potent inhibitor of galectin-3 expression, and holds great promise for use in inhibiting metastasis induced by elevated expression of galectin-3.

키워드

참고문헌

  1. Ali AM, Mackeen MM, Intan-Safinar I, Hamid M, Lajis NH, el-Sharkawy SH, Murakoshi M. 1996. Antitumour-promoting and antitumour activities of the crude extract from the leaves of Juniperus chinensis. J Ethnopharmacol 53:165-169 https://doi.org/10.1016/0378-8741(96)01434-1
  2. Azzam HS, Arand G, Lippman ME, Thompson EW. 1993. Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production. J Natl Cancer Inst 85:1758-1764 https://doi.org/10.1093/jnci/85.21.1758
  3. Bae KH. 2000. Medicinal Plants of Korea, Kyohaksa, Seoul. pp. 39
  4. Bae YS, Si CL, Kim JK, Darchesy JJ. 2005. Extractive of Juniper needle. J Kor For En 24:24-30
  5. Bresalier RS, Mazurek N, Sternberg LR, Byrd JC, Yunker CK, Nangia-Makker P, Raz A. 1998. Metastasis of human colon cancer is altered by modifying expression of the beta-galactosidebinding protein galectin 3. Gastroenterology 115:287-296 https://doi.org/10.1016/S0016-5085(98)70195-7
  6. Coli A, Bigotti G, Zucchetti F, Negro F, Massi G. 2002. Galectin- 3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia. Histopathology 40:80-87 https://doi.org/10.1046/j.1365-2559.2002.01304.x
  7. Dumic J, Dabelic S, Floel M. 2002. Curcumin: A potent inhibitor of galectin-3 expression. Food Technol Biotechnol 40:281-287
  8. Gabius HJ. 1997. Animal lectins. Eur J Biochem 243:543-576 https://doi.org/10.1111/j.1432-1033.1997.t01-1-00543.x
  9. Honjo Y, Inohara H, Akahani S, Yoshii T, Takenaka Y, Yoshida J, Hattori K, Tomiyama Y, Raz A, Kubo T. 2000. Expression of cytoplasmic galectin-3 as a prognostic marker in tongue carcinoma. Clin Cancer Res 6:4635-4640
  10. Honjo Y, Nangia-Makker P, Inohara H, Raz A. 2001. Downregulation of galectin-3 suppresses tumorigenicity of human breast carcinoma cells. Clin Cancer Res 7:661-668
  11. Hughes RC. 1999. Secretion of the galectin family of mammalian carbohydrate-binding proteins. Biochim Biophys Acta 1473: 172-185 https://doi.org/10.1016/S0304-4165(99)00177-4
  12. Jin MH, Park SG, Hwang YL, Lee MH, Jeong NJ, Roh SS, Lee Y, Kim CD, Lee JH. 2012. Cedrol enhances extracellular matrix production in dermal fibroblasts in a MAPK-dependent manner. Ann Dermatol 24:16-21 https://doi.org/10.5021/ad.2012.24.1.16
  13. Juliao SF, Rand N, Schwartz HS. 2002. Galectin-3: A biologic marker and diagnostic aid for chordoma. Clin Orthop Relat Res 397:70-75 https://doi.org/10.1097/00003086-200204000-00010
  14. Kagawa D, Jokura H, Ochiai R, Tokimitsu I, Tsubone H. 2003. The sedative effects and mechanism of action of cedrol inhalation with behavioral pharmacological evaluation. Planta Med 69:637-641 https://doi.org/10.1055/s-2003-41114
  15. Kim SJ, Jung JY, Kim HW, Park T. 2008. Anti-obesity effects of Juniperus chinensis extract are associated with increased AMP-activated protein kinase expression and phosphorylation in the visceral adipose tissue of rats. Biol Pharm Bull 31:1415-1421 https://doi.org/10.1248/bpb.31.1415
  16. Kim SJ, Shin JY, Lee KD, Bae YK, Choi IJ, Park SH, Chun KH. 2011. Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1). PLoS One 6:e25103 https://doi.org/10.1371/journal.pone.0025103
  17. Kim YW, Ko YT, Kim NK, Chung HC, Min BS, Lee KY, Park JP, Kim H. 2010. A comparative study of protein expression in primary colorectal cancer and synchronous hepatic metastases: The significance of matrix metalloproteinase-1 expression as a predictor of liver metastasis. Scand J Gastroenterol 45:217-225 https://doi.org/10.3109/00365520903453158
  18. Lim JP, Song YC, Kim JW, Ku CH, Eun JS, Leem KH, Kim DK. 2002. Free radical scavengers from the heartwood of Juniperus chinensis. Arch Pharm Res 25:449-452 https://doi.org/10.1007/BF02976600
  19. Loizzo MR, Tundis R, Menichini F, Saab AM, Statti GA, Menichini F. 2008. Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell Prolif 41:1002-1012 https://doi.org/10.1111/j.1365-2184.2008.00561.x
  20. Manter DK, Kelsey RG, Karchesy JJ. 2007. Antimicrobial activity of extractable conifer heartwood compounds toward Phytophthora ramorum. J Chem Ecol 33:2133-2147 https://doi.org/10.1007/s10886-007-9368-0
  21. Moon SH, Park KY. 2000. Antioxidative effect of persimmon leaves. Korean J Food & Nutr 13:53-58
  22. Nakamura M, Inufusa H, Adachi T, Aga M, Kurimoto M, Nakatani Y, Wakano T, Nakajima A, Hida JI, Miyake M, Shindo K, Yasutomi M. 1999. Involvement of galectin-3 expression in colorectal cancer progression and metastasis. Int J Oncol 15:143-148
  23. O'Brien S, Kay NE. 2011. Maintenance therapy for B-chronic lymphocytic leukemia. Clin Adv Hematol Oncol 9:22-31
  24. Plzak J, Smetana K Jr, Hrdlickova E, Kodet R, Holikova Z, Liu FT, Dvorankova B, Kaltner H, Betka J, Gabius HJ. 2001. Expression of galectin-3-reactive ligands in squamous cancer and normal epithelial cells as a marker of differentiation. Int J Oncol 19:59-64
  25. Song YK, Billiar TR, Lee YJ. 2002. Role of galectin-3 in breast cancer metastasis: involvement of nitric oxide. Am J Pathol 160:1069-1075 https://doi.org/10.1016/S0002-9440(10)64927-9
  26. Suh SJ, Kim JR, Jin UH, Choi HS, Chang YC, Lee YC, Kim SH, Lee IS, Moon TC, Chang HW, Kim CH. 2009. Deoxypodophyllotoxin, flavolignan, from Anthriscus sylvestris Hoffm inhibits migration and MMP-9 via MAPK pathways in TNF-alpha-induced HASMC. Vascul Pharmacol 51:13-20 https://doi.org/10.1016/j.vph.2008.10.004
  27. Sung JY, Yoon TJ, Yu KW, Lee KH, Lee H. 2006. Enhancement of immunological activities in mice by oral administration of pectic polysaccharides from Eleutherococcus senticosus. Food Sci Biotechnol 15:117-121
  28. Tester AM, Ruangpanit N, Anderson RL, Thompson EW. 2000. MMP-9 secretion and MMP-2 activation distinguish invasive and metastatic sublines of a mouse mammary carcinoma system showing epithelial-mesenchymal transition traits. Clin Exp Metastasis 18:553-560 https://doi.org/10.1023/A:1011953118186
  29. Woo HJ, Lotz MM, Jung JU, Mercurio AM. 1991. Carbohydratebinding protein 35 (Mac-2), a laminin-binding lectin, forms functional dimers using cysteine. J Biol Chem 266:18419- 18422
  30. Woo HJ, Shaw LM, Messier JM, Mercurio AM. 1990. The major non-integrin laminin binding protein of macrophage is identical to carbohydrate-binding protein 35 (Mac-2). J Biol Chem 265:7079-7099
  31. Woo JY, Paek NS, Kim YM. 2005. Studies on antioxidative effect and lactic acid bacteria growth of persimmon leaf extracts. Korean J Food & Nutr 18:28-38
  32. Yang RY, Hsu DK, Liu FT. 1996. Expression of galectin-3 modulates T-cell growth and apoptosis. Proc Natl Acad Sci USA 93:6737-6742 https://doi.org/10.1073/pnas.93.13.6737
  33. Yook CS. 1981. Medical Plants of Korea. Jinmyeong, Seoul. pp. 17
  34. Yoshii T, Inohara H, Takenaka Y, Honjo Y, Akahani S, Nomura T, Raz A, Kubo T. 2001. Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma cells. Int J Oncol 18:787-792

피인용 문헌

  1. 전기방사를 이용한 향나무 추출물 함유 PU 나노웹의 특성 vol.41, pp.1, 2012, https://doi.org/10.5850/jksct.2017.41.1.131