DOI QR코드

DOI QR Code

Iris Nertschinskia Ethanol Extract Differentially Induces Cytotoxicity in Human Breast Cancer Cells Depending on AKT1/2 Activity

  • Shin, Jae-Sik (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Maeng, Hyung-Gun (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Hong, Seung-Woo (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Moon, Jai-Hee (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Kim, Jin-Sun (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Suh, Young-Ah (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Kim, Eun-Sung (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Lee, Young-Min (PGR Assessment & Utilization Lab, National Agrobiodiversity Center (RDA Genebank)) ;
  • Kim, Ye-Seul (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Choi, Eun-Kyung (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Kim, Inki (Asan Institute for Life Science, Asan Medical Center) ;
  • Lee, Sok-Young (PGR Assessment & Utilization Lab, National Agrobiodiversity Center (RDA Genebank)) ;
  • Cho, Dong-Hyung (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Hong, Nam-Joo (School of Biotechnology, Yeungnam University) ;
  • Kim, Tae-Won (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Jin, Dong-Hoon (Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center) ;
  • Lee, Wang Jae (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
  • Published : 2012.12.31

Abstract

Recently, we reported that an ethanol extract of Iris nertschinskia induces p53-dependent apoptosis in the MCF7 human breast cancer cell line. However, the detailed mechanisms were not fully explored. Here, we demonstrate another aspect of the activity of I. nertschinskia in breast cancer cells. We compared the response to an ethanol extract of I. nertschinskia in two different human breast cancer cell lines, Hs578Tand MDA-MB231, respectively with relatively low and high AKT1/2 activity by trypan blue exclusion assay and FACS analysis. Knockdown of endogenous AKT1 or AKT2 in breast cancer cells by RNA interference determined the sensitivity to I. nertschinskia ethanol extract compared to control cells. The I. nertschinskia ethanol extract induced cell death in a manner that depended on the level of phosphorylated AKT1/2 protein and was associated with a significant increase in the sub-G1 cell population, indicative of apoptosis. Our results indicate that an ethanol extract of I. nertschinskia differentially induces cell death in breast cancer cells depending on their level of phosphorylated AKT1/2.

Keywords

Iris nertschinskia;AKT1;AKT2;breast cancer

Acknowledgement

Supported by : Asan Institute for Life Sciences

References

  1. Hers I, Vincent EE, Tavare JM (2011). Akt signalling in health and disease. Cell Signal, 23,1515-27. https://doi.org/10.1016/j.cellsig.2011.05.004
  2. Lee KH (2010). Discovery and development of natural product-derived chemotherapeutic agents based on a medicinal chemistry approach. J Nat Prod, 73, 500-16. https://doi.org/10.1021/np900821e
  3. Liu P, Cheng H, Roberts TM, et al (2009). Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov, 8, 627-44. https://doi.org/10.1038/nrd2926
  4. Lobenhofer EK, Huper G, Iglehart JD, et al (2000). Inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase activity in MCF-7 cells prevents estrogen-induced mitogenesis. Cell Growth Differ, 11, 99-110.
  5. Manning BD, Cantley LC (2007). AKT/PKB signaling: navigating downstream. Cell, 129, 1261-74. https://doi.org/10.1016/j.cell.2007.06.009
  6. Plas DR and Thompson CB (2005). Akt-dependent transformation: there is more to growth than just surviving. Oncogene, 24, 7435-42. https://doi.org/10.1038/sj.onc.1209097
  7. Rathmell JC, Fox CJ, Plas DR, et al (2003). Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival. Mol Cell Biol, 23, 7315-28. https://doi.org/10.1128/MCB.23.20.7315-7328.2003
  8. Sachsenmaier C (2001). Targeting protein kinases for tumor therapy. Onkologie, 24, 346-55. https://doi.org/10.1159/000055106
  9. Saif MW, Chu E (2010). Biology of colorectal cancer. Cancer J, 16,196-201. https://doi.org/10.1097/PPO.0b013e3181e076af
  10. Sarker D, Reid AH, Yap TA, et al (2009). Targeting the PI3K/ AKT pathway for the treatment of prostate cancer. Clin Cancer Res, 15, 4799-4805. https://doi.org/10.1158/1078-0432.CCR-08-0125
  11. Seo AM, Hong SW, Shin JS, et al (2009). Sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKK${\beta}$. Apoptosis, 14, 913-22. https://doi.org/10.1007/s10495-009-0367-1
  12. Shin JS, Hong SW, Lee JG, et al (2011). An ethanol extract of Iris nertschinskia induces p53-dependent apoptosis in the MCF7 human breast cancer cell line. Int J Mol Med, 27, 401-5.
  13. Simpson L, Parsons R (2001). PTEN: life as a tumor suppressor. Exp Cell Res, 264, 29-41. https://doi.org/10.1006/excr.2000.5130
  14. Steinegger E, Hansel R (1988). Lehrbuch der Phamakognosie und Phytopharmazie. Springer, Berlin Heidelberg New York pp414-21.
  15. Soung YH, Lee JW, Nam SW, et al (2006). Mutational analysis of AKT1, AKT2 and AKT3 genes in common human carcinomas. Oncology, 70, 285-9. https://doi.org/10.1159/000096289
  16. Tan TL, Wen JJ (2001). Pharmaceutical achievement of ShenNongBenCiaoJing. Chin Pharm J, 36, 349–50.
  17. Vivanco I, Sawyers CL (2002). The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer, 2, 489-501. https://doi.org/10.1038/nrc839
  18. Wollenweber E, Stevens JF, Klimo K, et al (2003). Cancer chemopreventive in vitro activities of isoflavones isolated from Iris germanica. Planta Med, 69, 15-20. https://doi.org/10.1055/s-2003-37030
  19. Wong SM, Oshima Y, Pezzuto JM, et al (1986). Isolation and characterization of a new from Iris missouriensis. J Nat Prod, 49, 330-3. https://doi.org/10.1021/np50044a024
  20. Ahmed NN, Grimes HL, Bellacosa A, et al (1997). Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci USA, 94, 3627-32. https://doi.org/10.1073/pnas.94.8.3627
  21. Bellacosa A, Kumar CC, Di Cristofano A, et al (2005). Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res, 94, 29-86. https://doi.org/10.1016/S0065-230X(05)94002-5
  22. Blagden S, Gabra H (2009). Promising molecular targets in ovarian cancer. Curr Opin Oncol, 21, 412-9. https://doi.org/10.1097/CCO.0b013e32832eab1f
  23. Chan TO, Rittenhouse SE, Tsichlis PN (1999). AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem, 68, 965-1014. https://doi.org/10.1146/annurev.biochem.68.1.965
  24. Chin YR and Toker A (2001). Akt isoform-specific signaling in breast cancer: uncovering an anti-migratory role for palladin. Cell Adh Migr, 5, 211-4.
  25. Datta SR, Brunet A, Greenberg ME (1999). Cellular survival: a play in three Akts. Gene Dev, 13, 2905-27. https://doi.org/10.1101/gad.13.22.2905
  26. Fang R, Houghton PJ, Hylands PJ (2008). Cytotoxic effects of compounds from Iris tectorumon human cancer cell lines. J Ethnopharmacol, 118, 257–63. https://doi.org/10.1016/j.jep.2008.04.006
  27. Franke TF, Yang SI, Chan TO, et al (1995). The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell, 81,727-36. https://doi.org/10.1016/0092-8674(95)90534-0
  28. Han J (1988). Traditional Chinese medicine and the search for new antineoplastic drugs. J Ethnopharmacol, 24, 1-17. https://doi.org/10.1016/0378-8741(88)90135-3

Cited by

  1. /M Phase and Growth Inhibition in SGC-7901 Gastric Cancer Cells vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6437
  2. Rana catesbeiana ribonuclease induces cell apoptosis via the caspase-9/-3 signaling pathway in human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.3117