Korean Journal of Plant Resources (한국자원식물학회지)

The Plant Resources Society of Korea (한국자원식물학회)
권호 표지
DOI QR코드

DOI QR Code

Berchemia floribunda-mediated Proteasomal Degradation of CyclinD1 via GKS3β-dependent Threonine-286 Phosphorylation in Human Colorectal Cancer Cells

인간 대장암 세포에 대한 먹넌출 추출물의 GSK3β 의존성 threonine-286 인산화를 통한 Cyclin D1 분해

  • Kang, Yeongyeong (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Eo, Hyun Ji (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Kim, Da Som (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Park, Youngki (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Song, Jeong Ho (Division of Special Forest Product, National Institute of Forest Science) ;
  • Park, Gwang Hun (Forest Medicinal Resources Research Center, National Institute of Forest Science)
  • 강연경 (국립산림과학원 산림약용자원연구소) ;
  • 어현지 (국립산림과학원 산림약용자원연구소) ;
  • 김다솜 (국립산림과학원 산림약용자원연구소) ;
  • 박영기 (국립산림과학원 산림약용자원연구소) ;
  • 송정호 (국립산림과학원 산림소득자원연구과) ;
  • 박광훈 (국립산림과학원 산림약용자원연구소)
  • Received : 2020.04.13
  • Accepted : 2020.04.29
  • Published : 2020.08.01
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the Berchemia floribunda (BF) which belongs to Rhamnaceae against human colorectal cancer cells. The treatment of BF decreased the cell proliferation in HCT116 cell and suppressed cellular accumulation of Cyclin D1 protein. Inhibition of proteasomal activity by MG132 attenuated BF-mediated Cyclin D1 downregulation and Cyclin D1 was decreased in the cell treated with BF. These findings indicates that BF-mediated Cyclin D1 downregulation may be result from Cyclin D1 proteasomal degradation. Additionally, BF-mediated Cyclin D1 degradation was blocked in the presence of LiCl, a GSK3β inhibitor, but not PD98059, SP600125, SB203580, Bay11-7082, LY294002 an ERK1/2 inhibitor, JNK inhibitor, p38 inhibitor, IκK inhibitor and PI3K inhibitor. Furthermore, BF phosphorylated Cyclin D1 at threonine-286 (Thr286), and LiCl-induced GSK3β inhibition reduced the BF mediated phosphorylation of Cyclin D1 at Thr286. These results suggested that BF may downregulate Cyclin D1 expression as a potential anti-cancer target through GSK3β dependent Cyclin D1 degradation. Therefore, this study provides that the extract of BF has anticancer activity against human colorectal cancer cells.

이상의 연구 결과로 먹넌출 열매 추출물은 GSK3β 의존성 Cyclin D1 단백질의 분해를 통해 대장암세포의 생육 억제와 관련이 있는 것으로 확인된다. 본 결과는 대장암의 항암제 개발을 위한 소재로 먹넌출 열매의 활용이 가능할 것으로 판단된다.

Keywords

References

  1. Alao, J.P. 2007. The regulation of cyclin D1 degradation: Roles in cancer development and the potential for therapeutic invention. Mol. Cancer 6:24. https://doi.org/10.1186/1476-4598-6-24
  2. Alt, J.R., J.L. Cleveland, M. Hannink and J.A. Diehl. 2000. Phosphorylation dependent regulation of cyclin D1 nuclear export and cyclin D1-dependent cellular transformation. Genes Dev. 14:3102-3114. https://doi.org/10.1101/gad.854900
  3. Bahnassy, A.A., A.R. Zekri, S. El-Houssini, A.M. El-Shehaby, M.R. Mahmoud, S. Abdallah and M. El-Serafi. 2004. Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients. BMC Gastroenterol. 4:22. https://doi.org/10.1186/1471-230X-4-22
  4. Dowdy, S.F., P.W. Hinds, K. Louis, S.I. Reed, A. Arnold and R.A. Weinberg. 1993. Physical interactions of the retinoblastoma protein with human cyclins. Cell 73:499. https://doi.org/10.1016/0092-8674(93)90137-F
  5. Gillett, C., V. Fantl, R. Smith, C. Fisher, J. Bartek, C. Dickson, D. Barnes and G. Peter. 1994. Amplication and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res. 54:1812-1817.
  6. Gopalakrishnan, N., M. Saravanakumar, P. Madankumar, M. Thiyagu and H. Devaraj. 2014. Colocalization of ${\beta}$-catenin with Notch intracellular domain in colon cancer: A possible role of Notch1 signaling in activation of cyclin D1-mediated cell proliferation. Mol. Cell. Biochem. 396:281-293. https://doi.org/10.1007/s11010-014-2163-7
  7. Han, S.H., H.Y. Kim, K.M. Park, M.S. Lee, H.J. Kim and Y.D. Kim. 1999. Expression of cyclin D1 protein in breast cancer and Its correlation with prognosis. J. Korean Surg. Soc. 56(6):771-776.
  8. Jemal, A., R. Siegel, E. Ward, T. Murray, J. Xu, C. Smigal and M.J. Thun. 2006. Cancer statistics. CA-Cancer J. Clin. 56:106-130. https://doi.org/10.3322/canjclin.56.2.106
  9. Jeong, J.B. and S.H. Lee. 2013. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells. Biochem. Biophys. Res. Commun. 430:381-386. https://doi.org/10.1016/j.bbrc.2012.11.018
  10. Jiang, W., S.M. Kahn, N. Tmita, Y.J. Zhang, S.H. Lu and I.B. Weinstein. 1992. Amplication and expression of the human cyclin D gene in esophageal cancer. Cancer Res. 52:2980-2983.
  11. Kim, H.N., J.D. Kim, H.J. Son, G.H. Park, H.J. Eo and J.B. Jeong. 2019. Anti-cancer activity of the leeave extracts of Rodgersia podophylla through ${\beta}$-catenin proteasomal degradation in human cancer cells. Korean J. Plant Res. 32(5):442-447.
  12. Kim, J.H. and M.Y. Kim. 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
  13. Kim, J.H., H.D. Cho, Y.S. Won, J.A. Heo, J.Y. Kim, H.G. Kim, S.H. Han, K.D. Moon and K.I. Seo. 2019. Inhibitory effects of Prunus mume solvent fractions on human colon cancer cells. J. Life Sci. 11:1227-1234.
  14. Kim, J.Y., E.J. Jung, Y.S. Won, J.H. Lee, D.Y. Shin and K.I. Seo. 2012. Cultivated Orostachys japonicus induces apoptosis in human colon cancer cells. Korean J. Food Sci. Technol. 44:317-323. https://doi.org/10.9721/KJFST.2012.44.3.317
  15. Korea National Arboretum (KNA). 2008. Rare plants data book in Korea. GEOBOOK, Seoul, Korea. p.186.
  16. Lanier, J. 2006. Alarming increase in Alaska natives. Int. J. Cancer 18:409-412. https://doi.org/10.1002/ijc.2910180403
  17. Lee, S.D., T.J. Lee and E.S. Park. 2008. Immunohistochemical analysis of nuclear factor, p38, and cyclin D1 proteins in premalignant lesions and carcinomas of the colorectal mucosa. Korean J. Gastroenterol. 52:359-367.
  18. Lee, S.W., Y.M. Kim and W.W. Kim. 2003. Lack of allozyme and ISSR variation in the rare endemic tree species, Berchemia berchemiaefolia (Rhamnaceae) in Korea. Ann. For. Sci. 60:357-360. https://doi.org/10.1051/forest:2003026
  19. Lee, T.H., H.K. Song, D.Y. Kim, I.S. Lee, H.H. Seo, J.Y. Choi, H.G. Kim, E.A. Choi and B.S. Han. 2018. Anti-cancer effect of Sarijang on colorectal cancer cells in a xenograft nude mouse model. Korean J. Food Sci. Technol. 50(4):451-456. https://doi.org/10.9721/KJFST.2018.50.4.451
  20. National Cancer Center. 2018. Annual report of cancer statistics in Korea in 2015. pp. 31-33.
  21. Ogino, S., K. Nosho, N. Irahara, S. Kure, K. Shima, Y. Baba, S. Toyoda, L. Chen, E.L. Giovannucci, J.A. Meyerhardt and C.S. Fuchs. 2009. A cohort study of cyclin D1 expression and prognosis in 602 colon cancer cases. Clin. Cancer Res. 15(13):4431-4438. https://doi.org/10.1158/1078-0432.CCR-08-3330
  22. Park, S.B., G.H. Park, H.M. Song, J.H. Park, M.S. Shin, H.J. Son, Y.R. Um and J.B. Jeong. 2017. Anti-proliferative activity of ethanol extracts of root of Aralia cordata var. continentalis through proteasomal degradation of cyclin D1 in human colorectal cancer cells. Korean J. Medicinal Crop Sci. 25(5):328-334. https://doi.org/10.7783/KJMCS.2017.25.5.328
  23. Qin, A., Q. Yu, Y. Gao, J. Tan, H. Huang, Z. Qiao and W. Qian. 2015. Inhibition of STAT3/cyclin D1 pathway promotes chemotherapeutic sensitivity of colorectal caner. Biochem. Biophys. Res. Commun. 457(4):681-687. https://doi.org/10.1016/j.bbrc.2015.01.048
  24. Sherr, C.J. 1993. Mammarian G1 cyclins. Cell 73:1059. https://doi.org/10.1016/0092-8674(93)90636-5
  25. Song, J.H., H.I. Lim, K.H. Jang and J.G. Han. 2013. Characteristics of leaf morphology and genetic variation of the rare woody plant, Berchemia racemosa var. magna. Korean J. Plant Res. 26(5):613-618. https://doi.org/10.7732/kjpr.2013.26.5.613
  26. Song, J.H., H.I. Lim, K.H. Jang, K.N. Hong and J.G. Han. 2014. Genetic diversity and spatial genetic structure of Berchemia racemosa var. magna in Anmyeon Island. Kor. J. Hort. Sci. Technol. 32(1):84-90.
  27. Stewart, B.W. and P. Kleihues. 2003. World Cancer Report. IARC Press, Lyon, France. pp. 183-187.
  28. Wang, H., T.O. Khor, L. Shu, Z. Su, F. Fuentes, J.H. Lee and A.N. Kong. 2012. Plants against cancer: A review on natural phytochemicals in preventing and treating cancers and their druggability. Anti-Cancer Agents Med. Chem. 12:1281-1305. https://doi.org/10.2174/187152012803833026
  29. Wang, Y.F., J.X. Cao, T. Efferth, G.F. Lai and S.D. Luo. 2006. Cytotoxic and new tetralone derivatives from Berchemia floribunda (Wall.) Brongn. Chem. Biodivers. 3(6):646-653. https://doi.org/10.1002/cbdv.200690067
  30. Yang, K., G. Yang, W.C. Stacey, J. Harwalkar, J. Fretthold, M. Hitomi and D.W. Stacey. 2006. Glycogen synthase kinase 3 has a limited role in cell cycle regulation of cyclin D1 levels. BMC Cell Biol. 7:33. https://doi.org/10.1186/1471-2121-7-33
  31. Zhang, Y.J., W. Jiang, C.J. Chene, C.S. Lee, S.M. Kahn, R.M. Santella and I.B. Weinstein. 1993. Amplication and overexpression of cyclin D1 in human hepatocellular carcinoma. Biochem. Biophys. Res. Commun. 196:1010-1016. https://doi.org/10.1006/bbrc.1993.2350