Skip to main content

Advertisement

SpringerLink
Log in

Potent apoptosis-inducing activity of erypoegin K, an isoflavone isolated from Erythrina poeppigiana, against human leukemia HL-60 cells

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

Erypoegin K is an isoflavone isolated from the stem bark of Erythrina poeppigiana. It contains a furan group at the A-ring of the core isoflavone structure and can inhibit the activity of glyoxalase I, an enzyme that catalyzes the detoxification of methylglyoxal (MG), a by-product of glycolysis. In the present study, we found that erypoegin K has a potent cytotoxic effect on human leukemia HL-60 cells. Its cytotoxic effect was much stronger than that of a known glyoxalase I inhibitor S-p-bromobenzylglutathione cyclopentyl diester. Conversely, erypoegin K demonstrated weak cytotoxicity toward normal human peripheral lymphocytes. The treatment of HL-60 cells with erypoegin K significantly induced caspase-3 activity, whereas the pretreatment of the cells with caspase-3 inhibitor suppressed erypoegin K-induced cell death. Furthermore, nuclear condensation and apoptotic genome DNA fragmentation were observed in erypoegin K-treated HL-60 cells. These results indicated that the observed cell death was mediated by apoptosis. In addition, the toxic compound MG was highly accumulated in the culture medium of erypoegin K-treated HL-60 cells, suggesting that cell apoptosis was triggered by extracellular MG. The present study showed that erypoegin K has a potent apoptosis-inducing effect on cancerous cell lines, such as HL-60.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Tanaka H, Etoh H, Shimizu H, Oh-Uchi T, Terada Y, Tateishi Y (2001) Erythrinan alkaloids and isoflavonoids from Erythrina poeppigiana. Planta Med 67:871–873

    Article  CAS  PubMed  Google Scholar 

  2. Tanaka H, Oh-Uchi T, Etoh H, Shimizu H, Tateishi Y (2002) Isoflavonoids from the roots of Erythrina poeppigiana. Phytochemistry 60:789–794

    Article  CAS  PubMed  Google Scholar 

  3. Tanaka H, Oh-Uchi T, Etoh H, Sako M, Sato M, Fukai T, Tateishi Y (2003) An arylbenzofuran and four isoflavonoids from the roots of Erythrina poeppigiana. Phytochemistry 63:597–602

    Article  CAS  PubMed  Google Scholar 

  4. Tanaka H, Etoh H, Kulkarni A, Fukai T (2004) Phenolic constituents and alkaloids from Erythrina species. Recent Res Devel Phytochem 8:83–116

    CAS  Google Scholar 

  5. Tanaka H, Oh-Uchi T, Nitanda T, Baba M, Etoh H, Shimizu H (2002) Prenylated cinnamylphenols, HIV-1 replication inhibitors, from Erythrina poeppigiana. Ite Lett Batter New Technol Med 3:612–615

    CAS  Google Scholar 

  6. Sato M, Tanaka H, Yamaguchi R, Oh-Uchi T, Etoh H (2003) Erythrina poeppigiana-derived phytochemical exhibiting antimicrobial activity against Candida albicans and methicillin-resistant Staphylococcus aureus. Lett Appl Microbiol 37:81–85

    Article  CAS  PubMed  Google Scholar 

  7. Sato M, Tanaka H, Tani N, Nagayama M, Yamaguchi R (2006) Different antibacterial actions of isoflavones isolated from Erythrina poeppigiana against methicillin-resistant Staphylococcus aureus. Lett Appl Microbiol 43:243–248

    Article  CAS  PubMed  Google Scholar 

  8. Hikita K, Yamada S, Shibata R, Katoh M, Murata T, Kato K, Tanaka H, Kaneda N (2015) Inhibitory Effect of isoflavones from Erythrina poeppigiana on the growth of HL-60 human leukemia cells through inhibition of glyoxalase I. Nat Prod Commun 10:1581–1584

    PubMed  Google Scholar 

  9. Djiogue S, Halabalaki M, Alexi X, Njamen D, Fomum ZT, Alexis MN, Skaltsounis A-L (2009) Isoflavonoids from Erythrina poeppigiana: evaluation of their binding affinity for the estrogen receptor. J Nat Prod 72:1603–1607

    Article  CAS  PubMed  Google Scholar 

  10. Djiogue S, Halabalaki M, Njamen D, Kretzschmar G, Lambrinidis G, Hoepping J, Raffaelli FM, Mikros E, Skaltsounis A-L, Vollmer G (2014) Erythroidine alkaloids: a novel class of phytoestrogens. Planta Med 80:861–869

    Article  CAS  PubMed  Google Scholar 

  11. Hikita K, Tanaka H, Murata T, Kato K, Hirata M, Sakai T, Kaneda N (2014) Phenolic constituents from stem bark of Erythrina poeppigiana and their inhibitory activity on human glyoxalase I. J Nat Med 68:636–642

    Article  CAS  PubMed  Google Scholar 

  12. Thornalley PJ (1990) The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochem J 269:1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Racker E (1951) The mechanism of action of glyoxalase. J Biol Chem 190:685–696

    CAS  PubMed  Google Scholar 

  14. Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270

    CAS  PubMed  Google Scholar 

  15. Rulli A, Carli L, Romani R, Baroni T, Giovannini E, Rosi G, Talesa V (2001) Expression of glyoxalase I and II in normal and breast cancer tissues. Breast Cancer Res Treat 66:67–72

    Article  CAS  PubMed  Google Scholar 

  16. Ranganathan S, Tew KD (1993) Analysis of glyoxalase-I from normal and tumor tissue from human colon. Biochim Biophys Acta 1182:311–316

    Article  CAS  PubMed  Google Scholar 

  17. Sakamoto H, Mashima T, Sato S, Hashimoto Y, Yamori T, Tsuruo T (2001) Selective activation of apoptosis program by S-p-bromobenzylglutathione cyclopentyl diester in glyoxalase I-overexpressing human lung cancer cells. Clin Cancer Res 7:2513–2518

    CAS  PubMed  Google Scholar 

  18. Hu X, Yang X, He Q, Chen Q, Yu L (2014) Glyoxalase 1 is up-regulated in hepatocellular carcinoma and is essential for HCC cell proliferation. Biotechnol Lett 36:257–263

    Article  CAS  PubMed  Google Scholar 

  19. Zhang S, Liang X, Zheng X, Huang H, Chen X, Wu K, Wang B, Ma S (2014) Glo1 genetic amplification as a potential therapeutic target in hepatocellular carcinoma. Int J Clin Exp Pathol 7:2079–2090

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bair WB 3rd, Cabello CM, Uchida K, Bause AS, Wondrak GT (2010) GLO1 overexpression in human malignant melanoma. Melanoma Res 20:85–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sakamoto H, Mashima T, Kizaki A, Dan S, Hashimoto Y, Naito M, Tsuruo T (2000) Glyoxalase I is involved in resistance of human leukemia cells to antitumor agent-induced apoptosis. Blood 95:3214–3218

    CAS  PubMed  Google Scholar 

  22. Thornalley PJ, Rabbani N (2011) Glyoxalase in tumourigenesis and multidrug resistance. Semin Cell Dev Biol 22:318–325

    Article  CAS  PubMed  Google Scholar 

  23. Tanaka T, Kuramitsu Y, Wang Y, Baron B, Kitagawa T, Tokuda K, Hirakawa K, Yashiro M, Naito S, Nakamura K (2013) Glyoxalase 1 as a candidate for indicating the metastatic potential of SN12C human renal cell carcinoma cell clones. Oncol Rep 30:2365–2370

    Article  CAS  PubMed  Google Scholar 

  24. Thornalley PJ, Edwards LG, Kang Y, Wyatt C, Davies N, Ladan MJ, Double (1996) Antitumour activity of S-p-bromobenzylglutathione cyclopentyl diester in vitro and in vivo. Inhibition of glyoxalase I and induction of apoptosis. Biochem Pharmacol 51:1365–1372

    Article  CAS  PubMed  Google Scholar 

  25. Vince R, Wadd WB (1969) Glyoxalase inhibitors as potential anticancer agents. Biochem Biophys Res Commun 35:593–598

    Article  CAS  PubMed  Google Scholar 

  26. Desai KM, Wu L (2008) Free radical generation by methylglyoxal in tissues. Drug Metabol Drug Interact 23:151–173

    Article  CAS  PubMed  Google Scholar 

  27. Kalapos MP (2008) The tandem of free radicals and methylglyoxal. Chem Biol Interact 171:251–271

    Article  CAS  PubMed  Google Scholar 

  28. Talukdar D (2008) A brief critical overview of the biological effects of methylglyoxal and further evaluation of a methylglyoxal-based anticancer formulation in treating cancer patients. Drug Metabol Drug Interact 23:175–210

    Article  CAS  PubMed  Google Scholar 

  29. Kang Y, Edwards LG, Thornalley PJ (1996) Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA G1 growth arrest and induction of apoptosis. Leuk Res 20:397–405

    Article  CAS  PubMed  Google Scholar 

  30. Okado A, Kawasaki Y, Hasuike Y, Takahashi M, Teshima T, Fujii J, Taniguchi N (1996) Induction of apoptotic cell death by methylglyoxal and 3-deoxyglucosone in macrophage-derived cell lines. Biochem Biophys Res Commun 225:219–224

    Article  CAS  PubMed  Google Scholar 

  31. Seo K, Ki SH, Shin SM (2014) Methylglyoxal induces mitochondrial dysfunction and cell death in liver. Toxicol Res 30:193–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chan WH, Wu HJ, Shiao NH (2007) Apoptotic signaling in methylglyoxal-treated human osteoblasts involves oxidative stress, c-Jun N-terminal kinase, caspase-3, and p21-activated kinase 2. J Cell Biochem 100:1056–1069

    Article  CAS  PubMed  Google Scholar 

  33. Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest Suppl 97:77–89

    CAS  PubMed  Google Scholar 

  34. Chaplen FWR, Fahl WE, Cameron DC (1996) Method for determination of free intracellular and extracellular methylglyoxal in animal cells grown in culture. Anal Biochem 238:171–178

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partly supported by a Grant-in-Aid for Scientific Research (C) (JP16K08311) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. Laboratory of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Yagotoyama 150, Tempaku, Nagoya, 468-8503, Japan

    Kiyomi Hikita, Natsuki Hattori, Aya Takeda, Yuko Yamakage, Rina Shibata, Saori Yamada, Tomiyasu Murata & Norio Kaneda

  2. Laboratory of Natural Product Chemistry, Faculty of Pharmacy, Meijo University, Yagotoyama 150, Tempaku, Nagoya, 468-8503, Japan

    Kuniki Kato & Hitoshi Tanaka

Authors
  1. Kiyomi Hikita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natsuki Hattori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aya Takeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuko Yamakage
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rina Shibata
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Saori Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kuniki Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tomiyasu Murata
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hitoshi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Norio Kaneda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norio Kaneda.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hikita, K., Hattori, N., Takeda, A. et al. Potent apoptosis-inducing activity of erypoegin K, an isoflavone isolated from Erythrina poeppigiana, against human leukemia HL-60 cells. J Nat Med 72, 260–266 (2018). https://doi.org/10.1007/s11418-017-1147-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-017-1147-9

Keywords

Search

Navigation