Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Sorghum Extract Enhances Caspase-dependent Apoptosis in Primary Prostate Cancer Cells and Immune Activity in Macrophages

수수 추출물에 의한 primary 전립선 암세포의 caspase 의존성 apoptosis 유도 및 대식세포 면역활성 증가

  • Cho, Hyun-Dong (Department of Food Science and Technology, Kyungpook National University) ;
  • Kim, Jeong-Ho (Department of Food and Nutrition, Sunchon National University) ;
  • Hong, Seong-Min (Department of Biotechnology, Dong-A University) ;
  • Lee, Ju-Hye (Functional Food and Nutrition Division, Department of Agro-Food Resource, National Academy of Agricultural Science, Rural Development Administration) ;
  • Lee, Yong-Seok (Department of Biotechnology, Dong-A University) ;
  • Kim, Du-Hyun (Department of Life Resources Industry, Dong-A University) ;
  • Seo, Kwon-Il (Department of Biotechnology, Dong-A University)
  • 조현동 (경북대학교 식품공학과) ;
  • 김정호 (순천대학교 식품영양학과) ;
  • 홍성민 (동아대학교 생명공학과) ;
  • 이주혜 (농촌진흥청 국립농업과학원 농식품자원부 기능성식품과) ;
  • 이용석 (동아대학교 생명공학과) ;
  • 김두현 (동아대학교 생명자원산업학과) ;
  • 서권일 (동아대학교 생명공학과)
  • Received : 2016.11.08
  • Accepted : 2016.12.06
  • Published : 2016.12.30
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Abstract

Sorghum bicolor L. is one of the important minor cereals in Asia, Africa, and the central United States, and it is considered a rich source of polyphenols, flavonoids, and dietary fiber. However, there is a lack of data on the anti-cancer activity of Sorghum in prostate cancer cells and immune activity in macrophages. This study aims to investigate the potential effects of an ethanol extract of S. bicolor L. (SE) on inducing apoptosis in RC-58T/h/SA#4 cells and immunomodulatory activity in RAW 264.7 cells. SE significantly inhibited the viability of RC-58T/h/SA#4 primary prostate cancer cells in a dose-dependent manner. The morphology of RC-58T/h/SA#4 cells treated with SE was shrunken and involved the formation of an apoptotic body and nuclear condensation. In addition, SE markedly activated caspase-8, -9, and -3; increased the protein levels of Bax, p53, cleaved PARP, and cytosolic cytochrome c; and decreased Bcl-2 protein expression. Furthermore, the inhibition of caspases in RC-58T/h/SA#4 cells with z-VAD-fmk attenuated SE-induced cell growth inhibition. The production of nitric oxide (NO) was also elevated by SE treatment, as revealed by immune response parameters. These results suggest that SE inhibits growth and induces apoptosis in primary human prostate cancer cells in a caspase-dependent manner, and it modulates the immune functions in macrophages. Therefore, Sorghum bicolor L. may be used as a functional food to prevent prostate cancer and enhance immune activity.

본 연구에서는 수수 에탄올 추출물(ethanol extract of Sorghum bicolor L., SE)을 이용하여 RC-58T/h/SA#4 primary 인체 전립선 암세포에 대한 apoptosis 유도효과 및 RAW 264.7 마우스 대식세포에 대한 면역활성 증진효능에 대해 알아보고자 하였다. SE의 처리는 RC-58T/h/SA#4 세포의 증식을 억제하였으며 세포수축을 통한 형태학적 변화를 유발하였다. 또한 apoptosis 관련 지표현상인 apoptotic body 및 핵의 형태변화를 관찰할 수 있었다. RC-58T/h/SA#4 세포에 SE를 처리하였을 때 caspase-8, -9, -3 단백질 활성을 증가시켰으며 pro-apoptotic 단백질인 Bax, p53, 분절된 PARP 및 세포질의 cytochrome c 단백질은 증가시킨 반면, anti-apoptotic 단백질인 Bcl-2 단백질은 감소시켰다. 이는 z-VAD-fmk로 caspase 활성을 억제시켰을 때 SE에 의한 세포증식 억제효과가 감소되었으며 이를 통해 SE에 의한 세포증식 억제효과는 caspase 의존적임을 확인할 수 있었다. 면역반응에서 nitric oxide(NO)의 증가는 면역활성 지표로 여겨지며, 본 연구에서 SE를 처리하였을 때 RAW 264.7 세포에서 NO 생성능이 증가하는 것으로 나타났다. 본 연구의 결과들은 SE가 primary 전립선 암세포에서 caspase 의존형 apoptosis를 유도하며 대식세포의 면역활성을 증가시킨다는 것을 나타낸다. 따라서 수수를 전립선 암 예방 및 면역활성을 증진효능이 있는 기능성 식품 소재로 활용할 수 있을 것으로 생각된다.

Keywords

References

  1. Byun, E. B., Jang, B. S., Sung, N. Y. and Byun, E. H. 2016. Immunomodulatory activity of crude polysaccharide separated from Cudrania tricuspidata leaf. J. Kor. Soc. Food Sci. Nutr. 45, 1099-1106. https://doi.org/10.3746/jkfn.2016.45.8.1099
  2. Chung, M. K. 2004. Review of the treatment outcome in the adenocarcinoma of the prostate. J. Kor. Med. Assoc. 47, 432-440. https://doi.org/10.5124/jkma.2004.47.5.432
  3. Darvin. P., Joung, Y. H., Nipin, S. P., Kang, D. Y., Byun, H. J., Hwang, D. Y., Cho, K. H., Park, K. D., Lee, H. K. and Yang, Y. M. 2015. Sorghum polyphenol suppresses the growth as well as metastasis of colon cancer xenografts through co-targeting jak2/STAT3 and PI3K/Akt/mTOR pathways. J. Funct. Foods 15, 193-206. https://doi.org/10.1016/j.jff.2015.03.020
  4. Dia, V. P., Pangloli, P., Jones, L., Mcclure, A. and Patel, A. 2016. Phytochemical concentrations and biological activities of Sorghum bicolor alcoholic extracts. Food Funct. 7, 3410-3420. https://doi.org/10.1039/C6FO00757K
  5. Fulda, S. and Debatin, K. M. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25, 4798-4811. https://doi.org/10.1038/sj.onc.1209608
  6. Grimmer, H. R., Parbhoo, V. and Mcgrath, R. M. 1992. Antimutagenicity of polyphenol-rich fractions from Sorghum bicolor grain. J. Sci. Food Agr. 59, 251-256. https://doi.org/10.1002/jsfa.2740590217
  7. Ha, J. H., Jeong, H. S., Jeong, M. H., Kim, S. S., Jin, L., Nam, J. H., Hwang, B., Ma, C. J. and Lee, H. Y. 2009. Comparison of anticancer activities of ultrasonification extracts of callus and roots from Rhodiola sachalinensis A. Bor. Kor. J. Food Sci. Technol. 41, 552-559.
  8. Kim, G. H., Lee, M. H., Han, M. H., Park, C., Hong, S. H. and Choi, Y. H. 2013. Induction of apoptosis by citri pericarpium methanol extract through reactive oxygen species generation in U937 human leukemia cells. J. Life Sci. 23, 1057-1063. https://doi.org/10.5352/JLS.2013.23.8.1057
  9. Kim, J. H. and Kim, M. Y. 2015. Anticancer effect of citrus fruit prepared by gamma irradiation of Budsticks. J. Life Sci. 25, 1051-1058. https://doi.org/10.5352/JLS.2015.25.9.1051
  10. Kim, J. Y., Noh, S. K., Woo, K. S. and Seo, M. C. 2016. Sorghum extract lowers lymphatic absorption of trans fat and cholesterol in rats. J. Kor. Soc. Food. Sci. Nutr. 45, 783-788. https://doi.org/10.3746/jkfn.2016.45.6.783
  11. Kim, K. O., Kim, H. S. and Ryu, H. S. 2006. Effect of Sorghum bicolor L. Moench (sorghum, su-su) water extracts on mouse immune cell activation. J. Kor. Diet Assoc. 12, 82-88.
  12. Kim, Y. E., Kwon, E. K., Han, D. S., Kim, I. H. and Ku, K. H. 2008. Antioxidant activity, fibrinolysis and angiotensin converting enzyme inhibitory activity of pine mushroom juice (Tricholoma matsutake Sing.). J. Kor. Soc. Food Sci. Nutr. 37, 535-541. https://doi.org/10.3746/jkfn.2008.37.5.535
  13. Kwak, C. S., Lim, S. J., Kim, S. A., Park, S. C. and Lee, M. S. 2004. Antioxidative and antimutagenic effects of Korean buckwheat, Sorghum, Millet and job's tears. J. Kor. Soc. Food Sci. Nutr. 33, 921-929. https://doi.org/10.3746/jkfn.2004.33.6.921
  14. Kwon, D. H., Kang, H. J., Choi, Y. H., Chung, K. T., Lee, J. H., Kang, K. H., Hyun, S. K., Kim, B. W. and Hwang, H. J. 2016. Immunomodulatory activity of water extract of Ulmus macrocarpa in Macrophages. J. Life Sci. 26, 50-58. https://doi.org/10.5352/JLS.2016.26.1.50
  15. Lee, J. H., Oh, E. K., Cho, H. D., Kim, J. Y., Lee, M. K. and Seo, K. I. 2013. Crude saponins from Platycodon grandiflorum induce apoptotic cell death in RC-58T/h/SA#4 prostate cancer cells through the activation of caspase cascades and apoptosis-inducing factor. Oncol. Rep. 29, 1421-1428. https://doi.org/10.3892/or.2013.2256
  16. Lee, J. W. and Kim, Y. H. 2011. Activation of pro-apoptotic multidomain Bcl-2 family member Bak and mitochondria-dependent caspase cascade are involved in p-coumaric acid-induced apoptosis in human jurkat T cells. J. Life Sci. 21, 1678-1688. https://doi.org/10.5352/JLS.2011.21.12.1678
  17. Lee, S. M., Choi, H. K. and Yu, G. H. 2003. Effect of bisphenol A, nonylphenol, pentachlorophenol on the proliferation of MCF-7 and PC-3 cells. Kor. J. Biotechnol. Bioeng. 18, 424-428.
  18. Park, H. Y., Lim, C. W., Kim, Y. K., Yoon, H. D. and Lee, K. J. 2006. Immunostimulating and anticancer activities of hot water extract from capsosiphon fulvescens. J. Kor. Soc. Appl. Biol. Chem. 49, 343-348.
  19. Sa, Y. J., Kim, J. S., Kim, M. O., Jeong, H. J., Yu, C. Y., Park, D. S. and Kim, M. J. 2010. Comparative study of electron donating ability, reducing power, antimicrobial activity and inhibition of ${\alpha}$-glucosidase by Sorghum bicolor extracts. Kor. J. Food Sci. Technol. 42, 598-604.
  20. Seo, M. C., Ko, J. Y., Song, S. B., Lee, J. S., Kang, J. R., Kwak, D. Y., Oh, B. G., Yoon, Y. N., Nam, M. H., Jeong, H. S. and Woo, K. S. 2011. Antioxidant compounds and activities of foxtail millet, proso millet and sorghum with different pulverizing methods. J. Kor. Soc. Food Sci. Nutr. 40, 790-797. https://doi.org/10.3746/jkfn.2011.40.6.790
  21. Siegel, R., Miller, K. and Jemal, A. 2015. Cancer statistics, 2015. CA Cancer J. Clin. 65, 5-29 https://doi.org/10.3322/caac.21254
  22. Wen, X., Lin, Z. Q., Liu, B. and Wei, Y. Q. 2012. Caspasemediated programmed cell death pathways as potential therapeutic targets in cancer. Cell Prolif. 45, 217-224. https://doi.org/10.1111/j.1365-2184.2012.00814.x
  23. Woo, K. S., Lee, J. S., Kang, J. R., Ko, J. Y., Song, S. B., Oh, B. G., Seo, M. C., Kwak, D. Y. and Nam, M. H. 2011. Effects of cultivated area on antioxidant compounds and antioxidant activities of sorghum (Sorghum biolor L. Moench. J. Kor. Soc. Food Sci. Nutr. 40, 1512-1517. https://doi.org/10.3746/jkfn.2011.40.11.1512
  24. Wyllie, A. H., Kerr, J. F. and Currie, A. R. 1980. Cell death: the significance of apoptosis. Int. Rev. Cytol. 68, 251-306. https://doi.org/10.1016/S0074-7696(08)62312-8