DOI QR코드

DOI QR Code

Lack of Cytotoxicity of the Colorant in Conjugated Linoleic Acid against Human Cancer and Normal Cells

Conjugated linoleic acid 황갈색의 인체암세포와 인체정상세포에 대한 세포독성

  • Ji, Yu-Chul (Division of Applied Life Sciences (BK21 Program), Graduate School, and Institute of Agriculture & Life Science, Gyeongsang National University) ;
  • Ahn, Chae-Rin (Division of Applied Life Sciences (BK21 Program), Graduate School, and Institute of Agriculture & Life Science, Gyeongsang National University) ;
  • Seo, Yang-Gon (Department of Chemical & Bioengineering, College of Engineering, Gyeongsang National University) ;
  • Suh, Jeong-Se (Department of Mechanical Engineering, Engineering Research Institute, College of Engineering, Gyeongsang National University) ;
  • Kim, Jeong-Ok (HK Biotech Co., Ltd.) ;
  • Ha, Yeong-Lae (Division of Applied Life Sciences (BK21 Program), Graduate School, and Institute of Agriculture & Life Science, Gyeongsang National University)
  • 지유철 (경상대학교 대학원 응용생명과학부) ;
  • 안채린 (경상대학교 대학원 응용생명과학부) ;
  • 서양곤 (경상대학교 화학생명공학과) ;
  • 서정세 (경상대학교 기계공학과) ;
  • 김정옥 ((주)HK바이오텍) ;
  • 하영래 (경상대학교 대학원 응용생명과학부)
  • Received : 2012.07.01
  • Accepted : 2012.08.09
  • Published : 2012.08.30

Abstract

The cytotoxicity of the colorant in conjugated linoleic acid (CLA) was investigated in human cancer cell lines and a normal human cell line. Commercially-available CLA with a brown color (designate crude CLA; c-CLA) was distilled in a vacuum (10 mmHg-$220^{\circ}C$, 10 mmHg-$235^{\circ}C$, 10 mmHg-$240^{\circ}C$, and 20 mmHg-$260^{\circ}C$) for 30 min to obtain pure CLA (distilled CLA; d-CLA) and dark brown-colored CLA (residual CLA; r-CLA) samples. No color intensity was shown in the d-CLA sample obtained under 10 mmHg-$220^{\circ}C$ conditions of distillation when the L (brightness), a (red/blue), and b (yellow/green) parameters were analyzed, whereas the r-CLA sample showed a dark brown color. The composition of CLA isomers in both the d- and r-CLA samples, as compared to that of the c-CLA sample, was not significantly different when analyzed by gas chromatography. When the cytotoxicity of the r-CLA and d-CLA samples obtained under 10 mmHg-$220^{\circ}C$ conditions were compared against human breast cancer cells (MCF-7), human lung cancer cells (A-549), human colon cancer cells (HT-29), human prostate cancer cells (PC-3), and human neuroblastoma cells (SK-N-SH), no significant cytotoxicity was seen in the cell lines. These results suggest that the color or colorant in the CLA samples did not have any effects on the proliferation of human cancer and normal cells and imply that the colorant in commercially available CLA samples is safe for human consumption.

체지방감소 효과가 있는 시판 conjugated linoleic acid (CLA)의 색깔을 제거하고 이 색깔의 세포독성에 관한 연구를 하였다. 황갈색의 시판 CLA 제품을 구입하여 crude CLA (c-CLA) 시료로 하였다. c-CLA 시료를 감압증류(10 mmHg-$220^{\circ}C$, 10 mmHg-$235^{\circ}C$, 10 mmHg-$240^{\circ}C$, 20 mmHg-$260^{\circ}C$; 30분)하여 증류된 CLA (distilled CLA; d-CLA) 시료와 증류되지 않고 남아있는 황갈색 CLA (residual CLA; r-CLA) 시료로 분리하였다. 10 mmHg-$220^{\circ}C$에서 증류하여 얻은 d-CLA 시료의 색깔은 L (brightness), a (red/blue), b (yellow/green)로 분석한 결과 무색에 가까웠고 r-CLA 시료는 황갈색이었고, 이들 두 CLA 시료의 CLA 이성체 조성은 변하지 않았다. 따라서 10 mmHg-$220^{\circ}C$에서 얻은 r-CLA 시료의 인체암세포(유방암 MCF-7. 폐암 A-549, 직장암 HT-29, 전립선암 PC-3)와 인체 정상세포(신경모세포 SK-N-SH)에 대한 세포독성을 d-CLA 시료와 비교하였다. 이들 암세포와 정상세포에 r-CLA 시료와 d-CLA 시료 처리 2일 후의 세포독성에는 차이가 없었다. 따라서 본 연구에서 c-CLA 시료에 함유된 색소는 10 mmHg-$220^{\circ}C$로 감압증류 하여 제거할 수 있었고, r-CLA 시료의 세포독성은 d-CLA 시료의 세포독성과 차이가 없었다. 이와 같은 결과는 c-CLA 시료에 함유된 색소는 세포생육에 아무런 영향을 미치지 않고 인체에 아무런 영향을 미치지 않음을 의미한다.

Keywords

References

  1. Albers, R., Van der Wielen, R. P. J., Brink, E. J., Hendriks, H. F. J., Doro- vska-Taran, V. N. and Mohede, I. C. M. 2003. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men. Eur. J. Clin. Nutr. 57, 595-603. https://doi.org/10.1038/sj.ejcn.1601585
  2. Beppu, F., Hosokawa, M., Tanaka, L., Kohno, H., Tanaka, T. and Miyashita, K. 2006. Potent inhibitory effect of trans9, trans11 isomer of conjugated linoleic acid on the growth of human colon cancer cells. J. Nutr. Biochem. 17, 830-836. https://doi.org/10.1016/j.jnutbio.2006.01.007
  3. Biaek, A., Tokarz, A., Dudek, A., Kazimierska, W. and Bielecki, W. 2010. Influence of diet enriched with conjugated linoleic acids on their distribution in tissues of rats with DMBA induced tumors. Lipids Health Dis. 9, 1-9. https://doi.org/10.1186/1476-511X-9-1
  4. Chen, S., Lin, Y., Huang, H., Hsu, W., Houng, J. and Huang, C. 2012. Effect of conjugated linoleic acid supplementation on weight loss and body fat composition in a Chinese population. Nutrition 28, 559-565. https://doi.org/10.1016/j.nut.2011.09.008
  5. Coakley, M., Ross, R. P., Nordgren, M., Fitzgerald, G., Devery, R. and Stanton, C. 2003. Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. J. Appl. Microbiol. 94, 138-145. https://doi.org/10.1046/j.1365-2672.2003.01814.x
  6. Ha, Y. L., Grimm, N. K. and Pariza, M. W. 1987. Anticarcinogens from fried ground beef: heat-altered derivatives of linoleic acid. Carcinogenesis 8, 1881-1887. https://doi.org/10.1093/carcin/8.12.1881
  7. Ha, Y. L. and Jeong, S. B. 2010. Effects of conjugated linoleic acid on body fat reduction and physical exercise enhancement of obese male middle school students. J. Life Sci. 20, 1844-1850. https://doi.org/10.5352/JLS.2010.20.12.1844
  8. Ha, Y. L., Storkson, J. and Pariza, M. W. 1990. Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid. Cancer Res. 50, 1097-1101.
  9. Halade, G. V., Rahman, M. M. and Fernandes, G. 2009. Effect of CLA isomers and their mixture on aging C57Bl/6J mice. Eur. J. Nutr. 48, 409-418. https://doi.org/10.1007/s00394-009-0029-7
  10. Hernandez-Mendoza, A., Lopez-Hernandez, A., Hill Jr, C. G. and Garcia, H. S. 2009. Bioconversion of linoleic acid to conjugated linoleic acid by Lactobacillus reuteri under different growth conditions. J. Chemical Technol. Biotechnol. 84, 180-185. https://doi.org/10.1002/jctb.2021
  11. Islam, M. A., Kim, Y. S., Jang, W. J., Lee, S. M., Kim, H. G., Kim, S. Y., Kim, J. O. and Ha, Y. L. 2008. A mixture of trans, trans conjugated linoleic acid induces apoptosis in MCF-7 human breast cancer cells with reciprocal expression of Bax and Bcl-2. J. Agric. Food Chem. 56, 5970-5976. https://doi.org/10.1021/jf8004977
  12. Jang, W. J. 2006. Production of natural CLA by submerged liquid culture of mushrooms. Master thesis, Gyeongsang National University, Jinju, Korea.
  13. Juaneda, P., De la Perriere, S., Sebedio, J. and Gregoire, S. 2003. Influence of heat and refining on formation of CLA isomers in sunflower oil. J. Am. Oil Chem. Soc. 80, 937-940. https://doi.org/10.1007/s11746-003-0800-3
  14. Kelley, N. S., Hubbard, N. E. and Erickson, K. L. 2007. Conjugated linoleic acid isomers and cancer. J. Nutr. 137, 2599-2607.
  15. Kim, Y. J. 2003. Partial inhibition of biohydrogenation of linoleic acid can increase the conjugated linoleic acid production of Butyrivibrio fibrisolvens A38. J. Agric. Food Chem. 51, 4258-4262. https://doi.org/10.1021/jf034057r
  16. Kim, S. J., Park, K. A., Jung, H. Y., Kim, J. O. and Ha, Y. L. 2000. Preparation of a large quantity of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers from synthetic CLA. J. Food Sci. Nutr. 5, 86-92.
  17. Kwon, J. M., Moon, Y. G., Kim, Y. S., Jung, J. Y., Ha. Y. L. and Yang, J. K. 2011. Effects of extraction methods of medicinal plants on the growth human of neuroblastoma SK-N-SH Cells. J. Life Sci. 21, 1190-1198. https://doi.org/10.5352/JLS.2011.21.8.1190
  18. Liavonchanka, A. and Feussner, I. 2008. Biochemistry of PUFA double bond isomerases producing conjugated linoleic acid. ChemBioChem. 9, 1867-1872. https://doi.org/10.1002/cbic.200800141
  19. Liu, G. and Chen. G. 2012. Study on the decolorization of biodiesel from waste cooking oil. Adv. Mater. Res. 347, 3781-3787.
  20. Mitchell, P. L., Langille, M. A., Currie, D. L. and McLeod, R. S. 2005. Effect of conjugated linoleic acid isomers on lipoproteins and atherosclerosis in the Syrian golden hamster. Biochim. Biophys. Acta. 1734, 269-276. https://doi.org/10.1016/j.bbalip.2005.04.007
  21. Ochoa, J. J., Farquharson, A. J., Grant, I., Moffat, L. E., Heys, S. D. and Wahle, K. W. J. 2004. Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: Different molecular mechanisms for cis-9, trans-11, and trans-10 cis-12 isomers. Carcinogenesis 25, 1185-1191. https://doi.org/10.1093/carcin/bgh116
  22. Park, S. J., Park, C. W., Kim, S. J., Kim, J. K., Kim, Y. R., Park, K. A., Kim, J. O. and Ha, Y. L. 2002. Methylation methods for the quantitative analysis of conjugated linoleic acid (CLA) isomers in various lipid samples. J. Agric. Food Chem. 50, 989-996. https://doi.org/10.1021/jf011185b
  23. Rakib, M. A., Kim, Y. S., Jang, W. J., Choi, B. D., Kim, J. O., Kong, I. K. and Ha, Y. L. 2010. Attenuation of 12-O-tetradecanoylphorbol- 13-acetate (TPA)-induced gap junctional intercellular communication (GJIC) inhibition in MCF-10A cells by c9,t11-conjugated linoleic acid. J. Agric. Food Chem. 58, 12022-12030. https://doi.org/10.1021/jf103205c
  24. Rakib, M. A., Kim, Y. S., Jang, W. J., Jang, J. S., Kang, S. J. and Ha, Y. L. 2011. Preventive effect of t,t-conjugated linoleic acid on 12-O-tetradecanoyl-phorbol-13-acetate-induced inhibition of gap junctional intercellular communication in human mammary epithelial MCF-10A Cells. J. Agric. Food Chem. 59, 4164-4170. https://doi.org/10.1021/jf1046909