Biomolecules & Therapeutics

  • 제27권2호
  • /
  • Pages.210-215
  • /
  • 2019
  • /
  • 1976-9148(pISSN)
  • /
  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
권호 표지
DOI QR코드

DOI QR Code

Gomisin G Suppresses the Growth of Colon Cancer Cells by Attenuation of AKT Phosphorylation and Arrest of Cell Cycle Progression

  • Maharjan, Sony (Center for Medical Science Research, College of Medicine, Hallym University) ;
  • Park, Byoung Kwon (Center for Medical Science Research, College of Medicine, Hallym University) ;
  • Lee, Su In (Center for Medical Science Research, College of Medicine, Hallym University) ;
  • Lim, Yoongho (Division of Bioscience and Biotechnology, BMIC, Konkuk University) ;
  • Lee, Keunwook (Department of Biomedical Science, College of Natural Science, Hallym University) ;
  • Lee, Younghee (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Kwon, Hyung-Joo (Center for Medical Science Research, College of Medicine, Hallym University)
  • 투고 : 2018.03.26
  • 심사 : 2018.05.17
  • 발행 : 2019.03.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins. Furthermore, Gomisin G remarkably triggered the accumulation of cells at the sub-G1 phase which represents apoptotic cells. In addition, the level of cyclin D1 and phosphorylated retinoblastoma tumor suppressor protein (Rb) was also reduced by the treatment with Gomisin G thus curtailing cell cycle progression. These findings show the suppressive effect of Gomisin G by inhibiting proliferation and inducing apoptosis in LoVo cells. Taken together, these results suggest Gomisin G could be developed as a potential therapeutic compound against colon cancer.

키워드

참고문헌

  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. Arnold, M., Sierra, M. S., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66, 683-691. https://doi.org/10.1136/gutjnl-2015-310912
  3. Boatright, K. M. and Salvesen, G. S. (2003) Mechanisms of caspase activation. Curr. Opin. Cell Biol. 15, 725-731. https://doi.org/10.1016/j.ceb.2003.10.009
  4. Chaitanya, G. V., Steven, A. J. and Babu, P. P. (2010) PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun. Signal. 8, 31. https://doi.org/10.1186/1478-811X-8-31
  5. Chen, D. F., Zhang, S. X., Xie, L., Xie, J. X., Chen, K., Kashiwada, Y., Zhou, B. N., Wang, P., Cosentino, L. M. and Lee, K. H. (1997) Anti-AIDS agents--XXVI. Structure-activity correlations of gomisin-G-related anti-HIV lignans from Kadsura interior and of related synthetic analogues. Bioorg. Med. Chem. 5, 1715-1723. https://doi.org/10.1016/S0968-0896(97)00118-1
  6. Choi, Y. W., Takamatsu, S., Khan, S. I., Srinivas, P. V., Ferreira, D., Zhao, J. and Khan, I. A. (2006) Schisandrene, a dibenzocyclooctadiene lignan from Schisandra chinensis: structure-antioxidant activity relationships of dibenzocyclooctadiene lignans. J. Nat. Prod. 69, 356-359. https://doi.org/10.1021/np0503707
  7. Danielsen, S. A., Eide, P. W., Nesbakken, A., Guren, T., Leithe, E. and Lothe, R. A. (2015) Portrait of the PI3K/AKT pathway in colorectal cancer. Biochim. Biophys. Acta 1855, 104-121.
  8. Darzynkiewicz, Z., Halicka, H. D. and Zhao, H. (2010) Analysis of cellular DNA content by flow and laser scanning cytometry. Adv. Exp. Med. Biol. 676, 137-147. https://doi.org/10.1007/978-1-4419-6199-0_9
  9. Engelman, J. A. (2009) Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 9, 550-562. https://doi.org/10.1038/nrc2664
  10. Fresno Vara, J. A., Casado, E., de Castro, J., Cejas, P., Belda-Iniesta, C. and Gonzalez-Baron, M. (2004) PI3K/Akt signalling pathway and cancer. Cancer Treat. Rev. 30, 193-204. https://doi.org/10.1016/j.ctrv.2003.07.007
  11. Ichim, G. and Tait, S. W. (2016) A fate worse than death: apoptosis as an oncogenic process. Nat. Rev. Cancer 16, 539-548. https://doi.org/10.1038/nrc.2016.58
  12. Jang, M. K., Yun, Y. R., Kim, J. H., Park, M. H. and Jung, M. H. (2017) Gomisin N inhibits adipogenesis and prevents high-fat diet-induced obesity. Sci. Rep. 7, 40345. https://doi.org/10.1038/srep40345
  13. Johnson, S. M., Gulhati, P., Rampy, B. A., Han, Y., Rychahou, P. G., Doan, H. Q., Weiss, H. L. and Evers, B. M. (2010) Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer. J. Am. Coll. Surg. 210, 767-768. https://doi.org/10.1016/j.jamcollsurg.2009.12.008
  14. Kaufmann, S. H., Desnoyers, S., Ottaviano, Y., Davidson, N. E. and Poirier, G. G. (1993) Specific proteolytic cleavage of poly(ADPribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res. 53, 3976-3985.
  15. Li, X. Q., Liu, X. X., Wang, X. Y., Xie, Y. H., Yang, Q., Ding, Y. Y., Cao, W. and Wang, S. W. (2017) Cinnamaldehyde derivatives inhibit coxsackievirus B3-induced viral myocarditis. Biomol. Ther. (Seoul) 25, 279-287. https://doi.org/10.4062/biomolther.2016.070
  16. Malinowsky, K., Nitsche, U., Janssen, K. P., Bader, F. G., Spath, C., Drecoll, E., Keller, G., Hofler, H., Slotta-Huspenina, J. and Becker, K. F. (2014) Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer. Br. J. Cancer 110, 2081-2089. https://doi.org/10.1038/bjc.2014.100
  17. Maharjan, S., Park, B. K., Lee, S. I., Lim, Y., Lee, K. and Kwon, H. J. (2018) Gomisin G inhibits the growth of triple-negative breast cancer cells by suppressing AKT phosphorylation and decreasing cyclin D1. Biomol. Ther. (Seoul) 26, 322-327. https://doi.org/10.4062/biomolther.2017.235
  18. Min, H. Y., Park, E. J., Hong, J. Y., Kang, Y. J., Kim, S. J., Chung, H. J., Woo, E. R., Hung, T. M., Youn, U. J., Kim, Y. S., Kang, S. S., Bae, K. and Lee, S. K. (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
  19. Moriarity, A., O'Sullivan, J., Kennedy, J., Mehigan, B. and McCormick, P. (2016) Current targeted therapies in the treatment of advanced colorectal cancer: a review. Ther. Adv. Med. Oncol. 8, 276-293. https://doi.org/10.1177/1758834016646734
  20. Navarro, M., Nicolas, A., Ferrandez, A. and Lanas, A. (2017) Colorectal cancer population screening programs worldwide in 2016: An update. World J. Gastroenterol. 23, 3632-3642. https://doi.org/10.3748/wjg.v23.i20.3632
  21. Newman, D. J. and Cragg, G. M. (2016) Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 79, 629-661. https://doi.org/10.1021/acs.jnatprod.5b01055
  22. Oh, S. Y., Kim, Y. H., Bae, D. S., Um, B. H., Pan, C. H., Kim, C. Y., Lee, H. J. and Lee, J. K. (2010) Anti-inflammatory effects of gomisin N, gomisin J, and schisandrin C isolated from the fruit of Schisandra chinensis. Biosci. Biotechnol. Biochem. 74, 285-291. https://doi.org/10.1271/bbb.90597
  23. Ogino, S., Nosho, K., Irahara, N., Kure, S., Shima, K., Baba, Y., Toyoda, S., Chen, L., Giovannucci, E. L., Meyerhardt, J. A. and Fuchs, C. S. (2009) A cohort study of cyclin D1 expression and prognosis in 602 colon cancer cases. Clin. Cancer Res. 15, 4431-4438. https://doi.org/10.1158/1078-0432.CCR-08-3330
  24. Opletal, L., Sovova, H. and Bartlova, M. (2004) Dibenzo[a,c]cyclooctadiene lignans of the genus Schisandra: importance, isolation and determination. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 812, 357-371. https://doi.org/10.1016/S1570-0232(04)00646-4
  25. Ormerod, M. G. (1998) The study of apoptotic cells by flow cytometry. Leukemia 12, 1013-1025. https://doi.org/10.1038/sj.leu.2401061
  26. Osaki, M., Oshimura, M. and Ito, H. (2004) PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9, 667-676. https://doi.org/10.1023/B:APPT.0000045801.15585.dd
  27. Park, H. J., Lee, S. J., Song, Y., Jang, S. H., Ko, Y. G., Kang, S. N., Chung, B. Y., Kim, H. D., Kim, G. S. and Cho, J. H. (2014) Schisandra chinensis prevents alcohol-induced fatty liver disease in rats. J. Med. Food 17, 103-110. https://doi.org/10.1089/jmf.2013.2849
  28. Parrish, A. B., Freel, C. D. and Kornbluth, S. (2013) Cellular mechanisms controlling caspase activation and function. Cold Spring Harb. Perspect. Biol. 5, a008672.
  29. Qie, S. and Diehl, J. A. (2016) Cyclin D1, cancer progression, and opportunities in cancer treatment. J. Mol. Med. 94, 1313-1326. https://doi.org/10.1007/s00109-016-1475-3
  30. Ryu, E. Y., Park, S. Y., Kim, S. G., Park, D. J., Kang, J. S., Kim, Y. H., Seetharaman, R., Choi, Y. W. and Lee, S. J. (2011) Anti-inflammatory effect of heme oxygenase-1 toward Porphyromonas gingivalis lipopolysaccharide in macrophages exposed to gomisins A, G, and J. J. Med. Food 14, 1519-1526. https://doi.org/10.1089/jmf.2011.1656
  31. Soldani, C. and Scovassi, A. I. (2002) Poly(ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 7, 321-328. https://doi.org/10.1023/A:1016119328968
  32. Shin, D. W., Kwon, Y. J., Ye, D. J., Baek, H. S., Lee, J. E. and Chun, Y. J. (2017) Auranofin suppresses plasminogen activator inhibitor-2 expression through annexin A5 induction in human prostate cancer cells. Biomol. Ther. (Seoul) 25, 177-185. https://doi.org/10.4062/biomolther.2016.223
  33. Sung, N. Y., Kim, S. C., Kim, Y. H., Kim, G., Lee, Y., Sung, G. H., Kim, J. H., Yang, W. S., Kim, M. S., Baek, K. S. and Cho, J. Y. (2016) Anti-proliferative and pro-apoptotic activities of 4-methyl-2,6-bis(1-phenylethyl)phenol in cancer cells. Biomol. Ther. (Seoul) 24, 402-409. https://doi.org/10.4062/biomolther.2015.166
  34. VanArsdale, T., Boshoff, C., Arndt, K. T. and Abraham, R. T. (2015) Molecular pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. Clin. Cancer Res. 21, 2905-2910. https://doi.org/10.1158/1078-0432.CCR-14-0816
  35. Vivanco, I. and Sawyers, C. L. (2002) The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat. Rev. Cancer 2, 489-501. https://doi.org/10.1038/nrc839
  36. Xiaoyang, L., Chenming, N., Chengqing, L. and Tao, L. (2015) Drugdrug interation prediction between ketoconazole and anti-liver cancer drug Gomisin G. Afr. Health Sci. 15, 590-593. https://doi.org/10.4314/ahs.v15i2.35

피인용 문헌

  1. Peritoneal Cells Mediate Immune Responses and Cross-Protection Against Influenza A Virus vol.10, 2019, https://doi.org/10.3389/fimmu.2019.01160
  2. CMTM4 inhibits cell proliferation and migration via AKT, ERK1/2, and STAT3 pathway in colorectal cancer vol.51, pp.9, 2019, https://doi.org/10.1093/abbs/gmz084
  3. Anti-Proliferative Activity of Nodosin, a Diterpenoid from Isodon serra, via Regulation of Wnt/β-Catenin Signaling Pathways in Human Colon Cancer Cells vol.28, pp.5, 2019, https://doi.org/10.4062/biomolther.2020.003
  4. Novel Anti-Angiogenic and Anti-Tumour Activities of the N-Terminal Domain of NOEY2 via Binding to VEGFR-2 in Ovarian Cancer vol.29, pp.5, 2019, https://doi.org/10.4062/biomolther.2021.121