Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory Effect of Linum usitatissimum and Perilla frutescens as Sources of Omega-3 Fatty Acids on Mutagenicity and Growth of Human Cancer Cell Lines

식물성 오메가-3계 지방산 급원인 아마씨 및 들깨의 항돌연변이 및 암세포 증식 억제 효과

  • Lim, Sun-Young (Division of Marine Environment & Bioscience, Korea Maritime University)
  • 임선영 (한국해양대학교 해양환경생명과학부)
  • Published : 2009.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

It has been known that Linum usitatissimum and Perilla frutescens are dietary sources of possible chemopreventive compounds such as lignans and $\alpha$-linolenic acid. Here, we investigated and compared the inhibitory effects of methanol extracts from Linum usitatissimum and Perilla frutescens on mutagenicity using the Ames test, and growth of human cancer cells (AGS human gastric adenocarcinoma, HT-29 human colon cancer, Hep 3B hepatocellular carcinoma cells). In the Ames test system using Salmonella typhimurium TA100, aflatoxin $B_1$ ($AFB_1$)-induced mutagenicity was significantly inhibited by treatment with the methanol extract from either Linum usitatissimum or Perilla frutescens (p<0.05) in a dose dependent manner. As for N-methyl-N'-nitro-N-nitrosoguamidine (MNNG)-induced mutagenicity, the methanol extracts (5 mg/assay) from Linum usitatissimum and Perilla frutescens showed 63% and 78% inhibitory rates, respectively, indicating that Perilla frutescens possessed stronger antimutagenic activity than did Linum usitatissimum. Inhibitory effects of methanol extracts from Linum usitatissimum and Perilla frutescens on the growth of human cancer cells (AGS, HT-29 and Hep 3B) appeared to increase dose dependently, and the inhibition was more effective against AGS and HT-29 compared to Hep 3B cells. Our results suggested that the methanol extract from Perilla frutescens showed stronger antimutagenic activity than that from Linum usitatissimumas assayed by the Ames mutagenic test, whereas the methanol extract from Linum usitatissimum was more effective than its counterpart for growth inhibition of human cancer cells. It is concluded that intake of Linum usitatissimum and Perilla frutescens as sources of omega-3 fatty acids will be beneficial for preventing cancer.

본 연구에서는 식물 종자들 중에서 특히 $\alpha$-linolenic acid의 급원으로 대표적인 아마씨와 들깨를 중심으로 Ames 실험을 이용한 돌연변이 유발 및 인체 암세포 증식 억제 효과에 대해 비교 검토하였다. 간접돌연변이 $AFB_1$ (0.7 mg/plate)에 대해 들깨 메탄올 추출물은 농도의 증가와 더불어 돌연변이 억제효과가 증가하였다. 첨가농도 2.5 및 5 mg/plate일 때 각각 86% 및 94%의 돌연변이 억제 효과를 나타내었다. 아마씨 메탄올 추출물의 경우도 첨가농도 2.5 및 5 mg/plate일 때 각각 74% 및 75%의 항돌연변이 효과를 보였다. 직접 돌연변이인 MNNG (0.6 mg/plate)에 대한 들깨 및 아마씨 메탄올 추출물의 항돌연변이성 실험을 한 결과, 첨가농도 1.25 mg/plate일 때부터 활성이 나타나 5 mg/plate 일 때는 각각 78, 63%의 돌연변이 억제 효과를 나타내었다. S. typhimurium TA100 균주에 대한 $AFB_1$과 MNNG의 돌연변이 유발실험에서 두 가지 종자인 들깨와 아마씨는 직접돌연변이원에 대해서보다는 간접돌연변이원에 의해 유발된 돌연변이 저해에 더 효과적이었으며 들깨에 의한 항돌연변이 효과가 더 우수하였음을 관찰할 수가 있었다. 한편, 아마씨 메탄올 추출물을 0.5, 1, 2 mg/ml의 농도별로 인체 위암세포(AGS)에 처리했을 때 농도 의존적으로 암세포 증식 억제 효과가 증가하여 1 mg/ml 첨가농도에서 64%의 암세포 성장 억제 효과를 보였고, 2 mg/ml 농도에서 79%의 높은 암세포 증식 억제 효과를 나타내었다. 들깨 메탄올 추출물의 경우도 아마씨 메탄올 추출물과 유사하게 농도의존적으로 암세포의 증식을 억제시켰으며 첨가농도 2 mg/ml일 때 68%의 증식 억제효과를 살펴 볼 수가 있었다. 인체 결장암세포(HT-29)의 경우, AGS 세포에 처리했을 때처럼 아마씨 메탄올 추출물은 첨가농도 0.5 mg/ml에서부터 활성을 타나내어 첨가농도 2 mg/ml에서는 72%의 암세포 증식 억제효과를 나타내었다. 들깨 메탄올 추출물의 경우 첨가농도 0.5 mg/ml에서는 43%의 억제효과를 나타내었으나 첨가농도 2 mg/ml에서는 64%로 결장암세포의 증식을 억제시켰다. 인체 간암세포(Hep 3B)에 의한 증식 억제효과는 이상의 암세포에 대한 효과보다 다소 낮았으나 아마씨 및 들깨 메탄올 추출물은 첨가농도 2 mg/ml에서 각각 65% 및 59%의 저해효과를 나타내었다.

Keywords

References

  1. Ames, B. N., J. McGann, and E. Yamasaki. 1975. Method for detecting carcinogens and mutagens with the SaImonellsa/mammalian-microsome mutagenicity test. Muta. Res. 31, 347-364 https://doi.org/10.1016/0165-1161(75)90046-1
  2. Bommareddy, A., X. Zhang, D. Schrader, R. S. Kaushil, D. Zeman, D. P. Matthees, and C. Dwivedi. 2009. Effects of dietary flaxseed on intestinal tumorigenesis in Apc (Min) mouse. Nutr. Cancer 61, 276-283 https://doi.org/10.1080/01635580802419764
  3. Cognault, S., M. L. Jourdan, E. Germain, R. Pitavy, E. Morel, G. Durand, P. Bougnoux, and C. Lhuillery. 2000. Effect of an a-linolenic acid-rich diet on rat mammary tumor growth depends on the dietary oxidative status. Nutr. Cancer 36, 33-41 https://doi.org/10.1207/S15327914NC3601_6
  4. Dwivedi, c., K. Natarajan, and D. P. Mattees. 2005. Chemopreventive effects of dietary flaxseed oil on colon tumor development. Nutr. Cancer 51, 52-58 https://doi.org/10.1207/s15327914nc5101_8
  5. Franceschi, R. T., W. M. James, and G. Zerlauth. 1985. 1$\alpha$, 25-dihydroxy vitamin D3 specific regulation of growth, morphology and fibronectin and a human osteosarcoma cell line. J. Cell PhysioI. 123, 401-409 https://doi.org/10.1002/jcp.1041230316
  6. Goldburg, E., H. Nitowsky, and S. Colowick. 1965. The role of glycolysis in the growth of tumor cells. J. BioI. Chem. 240, 2791-2796
  7. Hirose, M., A. Masuda, N. Ito, K. Kamano, and H. Okuyama. 1990. Effects of dietary perilla oil, soybean oil and safflower oil on 7,12-dimethylbenz [a] anthracene (DMBA) and l,2-dimethy-hydrazine (DMH)-induced mammary gland and colon carcinogenesis in female SD rats. Carcinogenesis 11, 731-735 https://doi.org/10.1093/carcin/11.5.731
  8. Hong, E. Y., H. J. Kang, C. S. Kwon, Y. J. Nam, M. J. Suh, and J. S. Kim. Modulation of cellular quinone reductase induciblity by roasting treatment and acid hydrolysis of perilla. J. Kor. Soc. Food Sci. Nutr. 26, 186-192
  9. Jelinska, M., A Tokarz, R. Oledzka, and A Czorniuk-Sliwa. 2003. Effects of dietary linseed, evening primose or fish oils on fatty acid and prostaglandin E2 contents in the rat livers and 7,12-dimethylbenz[a]anthracene-induced tumores. Biochim. Biophys. Acta 1637, 193-199 https://doi.org/10.1016/S0925-4439(03)00020-6
  10. Karp, F., C. A Mihaliak, J. L. Harri, and R. Croteau. 1990. Monoterpene biosynthesis specificity of the hydroxylactions of (-)-limonene by enzyme preparations from peppermint (Mentha spicata), and perilla (Perilla jrutescens) leaves. Arch. Biochem. Biophys. 276, 219-226 https://doi.org/10.1016/0003-9861(90)90029-X
  11. Kelley, D. S., G. J. Nelson, C. M. Serrato, P. C. Schmidt, and L. B. Branch. 1988. Effects of type of dietary fat on indices of immune status of rabbits. J. Nutr. 118, 1376-1384 https://doi.org/10.1016/S0271-5317(89)80057-0
  12. Kim, E. H. and D. H. Kim. 1981. Antioxidant activity of ethanol-extracts of defatted soybean, sesame, and perilla flours in a soybean oil-water emulsion system. Kor. J. Food Sci. Technol. 13, 283-288
  13. Kim, J. S., Y. J. Nam, and J. W. Kim. 1995. Screening of quinone reductase induces from agricultural byproducts using mouse hepatoma cell line. Kor. J. Food Sci. Technol. 27, 972-977
  14. Komaki, C., M. Okuno, N. Onogi, H. Moriwaki, T. Kawamori, T. Tanaka, H. Mori, and Y. Muto. 1996. Synergistic suppression of azoxymethane-induced foci of colonic aberrant crypts by the combination of $\beta$-carotene and perilla oil in rats. Carcinogenesis 17, 1897-1901 https://doi.org/10.1093/carcin/17.9.1897
  15. Kurowska, E. M., G. K Dresser, L. Deutsch, D. Vachon, and W. Khalil. 2003. Bioavailablity of omega-3 essential fatty acids. Prostaglandins Leukotrienes Essential Fatty Acids 68, 207-212 https://doi.org/10.1016/S0952-3278(02)00271-5
  16. Lee, Y. L D. H. Shin, Y. S. Chang, and J. I. Shin. 1993. Antioxidantvie effect of some edible plant solvent extracts with various synergists. Kor. J. Food Sci. Technol. 25, 683-688
  17. Maron, D. M. and B. N. Ames. 1983. Reversed methods for the Salmonella mutagenicity test. Muta. Res. 113, 173-215 https://doi.org/10.1016/0165-1161(83)90010-9
  18. Nagatsu, A, K Tenmaru, H. Matsuura, N. Murakami, T. Kobayashi, H. Okuyama, and J. Sakakibara. 1995. Novel antioxidants from roasted perilla seeds. Chem. Pharm. Bull. 43, 887-889 https://doi.org/10.1248/cpb.43.887
  19. Narisawa, T., M. Takahashi, H. Kotanagi, H. Kusaka, Y. Yamazaki, H. Koyama, Y. Fukaura, Y. Nishizawa, M. Kotsugai, Y. Isoda, J. Hirano, and N. Tanida. 1991. Inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid alpha-linoleic acid on colon carcinogenesis in rats. Jpn. J. Cancer Res. 82, 1089-1096 https://doi.org/10.1111/j.1349-7006.1991.tb01762.x
  20. Narisawa, T., Y. Fukaura, K Yazawa, C. Ishikawa, Y. Isoda, and Y. Nishizawa. 1994. Colon cancer prevention with a small amount of dietary perilla oil high in alpha-linolenic acid in an animal model. Cancer 15, 2069-2075
  21. Onogi, N., M. Okuno, C. Komaki, H. Moriwaki, T. Kawamori, T. Tanaka, H. Mori, and Y. Muto. 1996. Suppressing effect of perilla oil on azoxymethane-induced foci of clonic aberrant crypts in rats. Carcinogenesis 17, 1291-1296 https://doi.org/10.1093/carcin/17.6.1291
  22. Park W. K, B. H. Park and Y. H. Park. 2000. Encyclopedia of food and food science. Shin Kwang Publishibg Co. seoul Korea. pp. 234
  23. Park, D. S., K I. Lee, and K Y. Park. 2001. Quantitative analysis of dietary fibers from perilla frutescens seeds and antimutagenic effect of its extracts. J. Kor. Soc. Food Sci. Nutr. 30, 900-905
  24. Rose, D. P., J. M. Connolly, J. Rayburn, and M. Coleman. 1995. Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cnacer cells in nude mice. J. Natl. Cancer Inst. 87, 587-592 https://doi.org/10.1093/jnci/87.8.587
  25. Sandstrom, B., S. BugaeL C. Lauridsen, F. Nielsen, C. Jensen, and L. H. Skibsted. 2000. Cholesterol-lowering potential in human subjects of fat from pigs fed rapseed oil. Br. J. Nutr. 84, 143-150 https://doi.org/10.1016/S0946-672X(04)80033-6
  26. Thuy, N. T., P. He, and H. Takeuchi. 2001. Comparative effect of dietary olive, safflower, and linseed oils on spontaneous liver tumorigenesis in C3H/He mice. J. Nutr. Sci. Vitaminol. (Tokyo) 47, 363-366 https://doi.org/10.3177/jnsv.47.363
  27. Tou, J. C. L. and L. U. Thompson. 1999. Exposure to flaxseed or its lignan component during different developmental stages influences rat mammary gland structures. Carcinegenesis 20, 1831-1835 https://doi.org/10.1093/carcin/20.9.1831
  28. Wachi, AM., L. A Sinclair, R. G. Wilkinson, M. Enser, J. D. Wood, and A V. Fisher. 2002. Effect of dietary fat source and breed on the carcass composition, n-3 polyunsaturated and conjugated linoleic acid content of sheep meat and adipose tissue. Br. J. Nutr. 88, 697-709 https://doi.org/10.1079/BJN2002727
  29. Wang, L., J. Chen, and L. U. Thompson. 2005. The inhibitory effect of flaxseed on the growth and metastasis of estrogen receptor negative human breast cancer xenografts is attributed to both its lignan and oil components. Int. J. Cancerm. 116, 793-798 https://doi.org/10.1002/ijc.21067
  30. Watanabe, S., N. Sakai, Y. Yasui, Y. Kimura, T. Kobayashi, T. Mizutani, and H. Okuyama. 1994. A high a-linolenate diet suppresses antigen-induced immunoglobin E response and anaphylactic shock in mice. J. Nutr. 124, 1566-1573 https://doi.org/10.1016/0929-7855(95)00060-7
  31. Williams, D., M. Verghese, L. T. Walker, J. Boateng, L. Shackelford, and C. B. Chawan. 2007. Flax seed oil and flax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane-induced colon cancer in fisher 344 male rats. Food Chem. Toxicol. 45, 153-159 https://doi.org/10.1016/j.fct.2006.08.014
  32. Yan, L., J. A Yee, D. Li, M. H. McGuire, and L. U. Thompson. 1998. Dietary flaxeed supplementation and experimental metastasis of melanoma cells in mice. Cancer Lett. 124, 181-186 https://doi.org/10.1016/S0304-3835(97)00470-9
  33. Zaidi, N. H., P. J. O'Connor, and W. H. Butler. 1993. N-methyl-N' -nitro-N-nitrodoguamidine-induced carcinogenesis: differential pattern of upper gastointestinal tract tumours in Wistar rats after single or chronic oral doses. Carginogenesis 14, 1561-1567 https://doi.org/10.1093/carcin/14.8.1561

Cited by

  1. Comparison of Antioxidant and Anti-proliferative Activities of Perilla (Perilla frutescens Britton) and Sesame (Seasamum indicum L.) leaf extracts vol.29, pp.3, 2013, https://doi.org/10.9724/kfcs.2013.29.3.241
  2. Effect of Carrot Powder on Anti-Oxidative and Quality Characteristics of Perilla-Dasik vol.44, pp.12, 2015, https://doi.org/10.3746/jkfn.2015.44.12.1832
  3. An Establishment of the Optimum Sowing Time for a Machine Harvest of Perilla for Seed vol.30, pp.4, 2018, https://doi.org/10.12719/KSIA.2018.30.4.370