Journal of Life Science (생명과학회지)

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

DOI QR Code

Anti-proliferative and Pro-apoptotic Activities by Pomace of Schisandra chinensis (Turcz.) Baill. and Schizandrin

오미자 박 추출물 및 schizandrin에 의한 암세포 항성장 및 세포사멸 활성

  • Kim, Hyun-Ji (Department of Biological Sciences, Andong National University) ;
  • Seo, Yu-Mi (Department of Biological Sciences, Andong National University) ;
  • Lee, Eun-Ju (Department of Biological Sciences, Andong National University) ;
  • Chung, Chungwook (Department of Biological Sciences, Andong National University) ;
  • Sung, Hwa-Jung (Department of Food and Nutrition, Andong National University) ;
  • Sohn, Ho-Yong (Department of Food and Nutrition, Andong National University) ;
  • Park, Jong-Yi (Gyeongbuk Institute for Bio Indudustry) ;
  • Kim, Jong-Sik (Department of Biological Sciences, Andong National University)
  • 김현지 (국립안동대학교 생명과학과) ;
  • 서유미 (국립안동대학교 생명과학과) ;
  • 이은주 (국립안동대학교 생명과학과) ;
  • 정정욱 (국립안동대학교 생명과학과) ;
  • 성화정 (국립안동대학교 식품영양학과) ;
  • 손호용 (국립안동대학교 식품영양학과) ;
  • 박종이 (경북바이오산업 연구원) ;
  • 김종식 (국립안동대학교 생명과학과)
  • Received : 2017.10.19
  • Accepted : 2018.02.12
  • Published : 2018.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Schisandra chinensis (Turcz.) Baill. (omija) is often used in Chinese medicine to treat various human diseases, and is known to possess various bioactive components such as schizandrin and gomisin A. In the present study, we prepared ethanol extracts of pomace of Schisandra chinensis (PSC) and investigated their effects on cell viability and expression changes of pro-apoptotic genes such as ATF3, NAG-1 and p21 in human colorectal cancer HCT116 cells. PSC significantly reduced cell viability in a dose-dependent manner, and also dramatically induced the expression of ATF3, NAG-1 and p21 genes, with resveratrol used as a positive control. We also assessed the effects of pure compound schizandrin (SZ) derived from Schisandra chinensis on cell viability and expression of pro-apoptotic genes such as ATF3, NAG-1 and p21. The results showed that SZ also decreased cell viabilities in a dose-dependent manner and increased the expression of ATF3, NAG-1 and p21 genes. In addition, apoptosis was detected in SZ-treated HCT116 cells, which was confirmed with PARP cleavage. PARP cleavage was recovered in part by the transfection of NAG-1 siRNA. The results indicate that NAG-1 is one of the genes responsible for apoptosis induced by SZ. Overall, our findings may contribute to understanding the molecular mechanisms of anti-proliferative and pro-apoptotic activities mediated by PSC and SZ.

오미자는 다양한 인간 질환을 치료하기 위한 한약재로 사용되어 왔으며, schizandrin과 gomisin A와 같은 다양한 생리활성물질을 함유하고 있는 것으로 알려져 있다. 본 연구에서는 오미자 박으로부터 에탄올 추출물(PSC)을 제조하고, 이들이 대장암 세포인 HCT116의 세포 생존율에 미치는 영향과 ATF3, NAG-1, p21와 같은 pro-apoptotic 유전자의 발현 변화에 미치는 영향을 연구하였다. 오미자 박 에탄올 추출물의 처리는 농도 의존적으로 암세포생존율을 감소시켰으며, 세 가지 pro-apoptotic 유전자의 발현을 모두 증가시켰다. 또한, 오미자 유래의 순수물질인 schizandrin도 세포 생존율을 농도의존적으로 감소시켰으며, ATF3, NAG-1, p21 유전자의 발현을 증가시켰다. 게다가, schizandrin을 처리한 세포에서 PARP cleavage를 확인함으로써 apoptosis가 일어남을 확인하였다. 이러한 PARP cleavage는 NAG-1 siRNA의 transfection에 의해서 회복됨을 확인하였다. 이러한 결과는 schizandrin에 의해 유도되는 apoptosis와 NAG-1의 발현증가가 직접적인 관련이 있음을 나타낸다. 종합적으로, 본 연구결과는 오미자 박 추출물과 schizandrin에 의해 매개되는 항암 활성과 암세포 사멸현상을 이해하는데 도움을 줄 것으로 사료된다.

Keywords

References

  1. Cho, Y. J., Ju, I. S., Kim, B. C., Lee, W. S., Kim, M. J., Lee, B. G., An, B. J., Kim, J. H. and Kwon, O. J. 2007. Biological activity of Omija (Schizandra chinensis Baillon) extracts. J. Kor. Soc. Appl. Biol. Chem. 50, 198-203.
  2. Frank, G., Bottone, Jr. and Brenda, A. M. 2011. The dietary compounds resveratrol and genistein induce activating transcription factor 3 while suppressing inhibitor of DNA binding/differentiation-1. J. Med. Food 14, 584-593 https://doi.org/10.1089/jmf.2010.0110
  3. Guon, T. G. and Chung, H. S. 2014. Effects of Nelumbo nucifera root extract on proliferation and apoptosis in HT-29 human colon cancer cells. J. East Asian Soc. Dietary Life. 24, 20-27.
  4. Hu, X., Wang, J., Xia, Y, Simayi, M, Ikramullah, S., He, Y., Cui, S., Li, S. and Wushouer, Q. 2016. Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals. Mol. Med. Rep. 14, 5231-5236. https://doi.org/10.3892/mmr.2016.5884
  5. Kim, B. H., Cho, D. U., Han, K. S. and Bae, Y. L. 2011. Efficiency analysis of Schisandra tea using image & acoustic signal processing. Journal of Korea Academia Industrial Cooperation Society 12, 2975-2981. https://doi.org/10.5762/KAIS.2011.12.7.2975
  6. Kim, J. S. and Choi, S. 2008. Physicochemical properties and antioxidative activities of Omija (Schizandra chinensis Bailon). Kor. J. Food Nutr. 21, 35-42.
  7. Kim, K. J., Lee, J., Park, Y. and Lee, S. H. 2015. ATF3 mediates anti-cancer activity of trans-10, cis-12-conjugated linoleic acid in human colon cancer cells. Biomol. Ther. (Seoul). 23, 134-140. https://doi.org/10.4062/biomolther.2014.107
  8. Kim, M. S., Sung, H. J., Park, J. Y. and Sohn, H. Y. 2017. Evaluation of anti-oxidant, anti-microbial and anti-thrombosis activities of fruit, seed and pomace of Schizandra chinensis Baillon. J. Life Sci. 27, 131-138. https://doi.org/10.5352/JLS.2017.27.2.131
  9. Lim, J. H., Park, J. W., Min, D. S., Chang, J. S., Lee, Y. H., Park, Y. B., Choi, K. S. and Kwon, T. K. 2007. NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells. Apoptosis 12, 411-421. https://doi.org/10.1007/s10495-006-0576-9
  10. Min, H., Park, E., Hong, J., Kang, Y., Kim, S., Chung, H., Woo, E., Hung, T. M., Youn, U. J. and Kim, Y. S. 2008. Antiproliferative effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis in human cancer cells. Bioorg. Med. Chem. Lett. 18, 523-526. https://doi.org/10.1016/j.bmcl.2007.11.082
  11. Park, G. H., Song, H. M. and Jeong, J. B. 2017. Kahweol from coffee induces apoptosis by upregulating activating transcription factor 3 in human colorectal cancer cells. Biomol. Ther. (Seoul). 25, 337-343. https://doi.org/10.4062/biomolther.2016.114
  12. Saul, R. B., Javier, F., Ignacio, G. R., Claudio, J. V. and Felipe, L. 2017. New Insights toward colorectal cancer chemotherapy using natural bioactive compounds. Front. Pharmacol. 8, 1-22.
  13. Seung, J. B., Leigh, C. W. and Thomas, E. E. 2002. Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53. Carcinogenesis 23, 425-434. https://doi.org/10.1093/carcin/23.3.425
  14. Shin, E. J., Chung, S. W. and Hwang, J. T., 2017. Effect of $\gamma$-oryzanol on proliferation and apoptosis of AGS human gastric carcinoma cell. KSBBJ 32, 83-89. https://doi.org/10.7841/ksbbj.2017.32.2.83
  15. Suh, W. S., Park, S. Y., Min, B. S., Kim, S. H., Song, J. H. and Shim, S. H. 2014. The anti-proliferative effects of compounds isolated from Schisandra chinensis. Kor. J. Food Sci. Technol. 46, 665-670. https://doi.org/10.9721/KJFST.2014.46.6.665
  16. Sun, S. Y., Hail, N. Jr. and Lotan, R. 2004. Apoptosis as a novel target for cancer chemoprevention. J. Natl. Cancer Inst. 96, 662-672. https://doi.org/10.1093/jnci/djh123
  17. Wilson, L. C., Baek, S. J., Call, A. and Eling, T. E. 2003. Nonsteroidal anti‐inflammatory drug‐activated gene (NAG‐1) is induced by genistein through the expression of p53 in colorectal cancer cells. Int. J. Cancer 105, 747-753. https://doi.org/10.1002/ijc.11173
  18. Yang, M. H., Kim, J., Khan, I. A., Walker, L. A. and Khan, S. I. 2014. Nonsteroidal anti-inflammatory drug activated gene-1 (NAG-1) modulators from natural products as anti-cancer agents. Life Sci. 100, 75-84. https://doi.org/10.1016/j.lfs.2014.01.075
  19. Yi, H., Chen, Y., Liu, J., Zhang, J., Guo, W., Xiao, W. and Yao, Y. 2016. Extraction and separation of active Ingredients in Schisandra chinensis (Turcz.) Baill and the study of their antifungal effects. PLoS One 11, e0154731. https://doi.org/10.1371/journal.pone.0154731
  20. Yoon, Y. S., Yu, C. S., Jung, S. H., Choi, P. W., Han, K. R., Kim, H. C. and Kim, J. C. 2007. Characteristics of colorectal cancer detected at the health promotion center. J. Kor. Soc. Coloproctol. 23, 321-326. https://doi.org/10.3393/jksc.2007.23.5.321
  21. Zhang, C., Gao, C., Kawauchi, J., Hashimoto, Y., Tsuchida N. and Kitajima, S. 2002. Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53. Biochem. Biophys. Res. Commun. 297, 1302-1310. https://doi.org/10.1016/S0006-291X(02)02382-3
  22. Zhang, Z., Wu, L., Wang, J., Li, G., Feng, D., Zhang, B., Li, L., Yang, J., Ma, L. and Qin, H. 2014. Opposing effects of PI3K/Akt and Smad-dependent signaling pathways in NAG-1-induced glioblastoma cell apoptosis. PloS One 9, e96283. https://doi.org/10.1371/journal.pone.0096283
  23. Zhu, H., Zhang, L., Wang, G., He, Z., Zhao, Y., Xu, Y., Gao, Y. and Zhang, L. 2016. Sedative and hypnotic effects of supercritical carbon dioxide fluid extraction from Schisandra chinensis in mice. J. Food Drug Anal. 24, 831-838. https://doi.org/10.1016/j.jfda.2016.05.005