Download PDF
Planta Med 2018; 84(14): 1038-1044
DOI: 10.1055/a-0578-8689
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

A Monoclonal Antibody-Based Enzyme-Linked Immunosorbent Assay for Determination of Homoharringtonine

Benyakan Pongkitwitoon   *
1   Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
,
Seiichi Sakamoto   *
2   Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
,
Rika Nagamitsu
2   Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
,
Waraporn Putalun
3   Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
4   Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), National Research University-Khon Kaen University, Khon Kaen, Thailand
,
Hiroyuki Tanaka
2   Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
,
Satoshi Morimoto
2   Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
› Author Affiliations
Further Information

Publication History

received 22 November 2017
revised 25 January 2018

accepted 15 February 2018

Publication Date:
28 February 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Homoharringtonine (HHT), also known as omacetaxine, is a natural compound found in the genus Cephalotaxus and is a promising pharmaceutical drug used for the treatment of chronic or accelerated phase chronic myeloid leukemia. As a tool for the quantitative determination of HHT, a specific monoclonal antibody against HHT (MAb 6A1) was generated by conjugates prepared via sodium periodate-mediated oxidation. The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) using MAb 6A1 was found to be highly specific and sensitive with a limit of detection for HHT of 48.8 ng/mL. Validation assays to evaluate precision and accuracy of the method were conducted by the use of intra- and inter-assay analysis, recovery test, and comparison analysis between the amounts of HHT determined by ELISA and high-performance liquid chromatography. These results revealed that the established icELISA using MAb 6A1 is specific, sensitive, and reliable enough to be applied to the qualitative analysis for HHT. Furthermore, the results of this study support the usefulness of sodium periodate as a reagent for the conjugation between Cephalotaxus alkaloids and proteins for producing specific antibodies.

Key words

Cephalotaxus harringtonii - enzyme-linked immunosorbent assay - homoharringtonine - monoclonal antibody - sodium periodate-mediated conjugation - Taxaceae

* These authors contributed equally to this work.


Supporting Information

    Dose-response curves of icELISA using MAb 6A1 to determine IC50 for CR of HT and cephalotaxine are available as Supporting Information.

  • Supporting Information
 

  • References

  • 1 Powell RG, Weisleder D, Smith jr. CR. Antitumor alkaloids from Cephalotaxus harringtonia: structure and activity. J Pharm Sci 1972; 61: 1227-1230
    CrossrefPubMedSearch in Google Scholar
  • 2 Moirangthem DS, Borah JC, Laishram S, Kalita MC, Talukdar NC. HPLC analysis of harringtonine and homoharringtonine in the needles of Cephalotaxus griffithii alkaloid fraction and cytotoxic activity on chronic myelogenous leukaemia K562 cell. Nat Prod Res 2014; 28: 1503-1506
    CrossrefPubMedSearch in Google Scholar
  • 3 Takemura Y, Ohmura T, Chou TC, Okano T, Holland JF. Biologic and pharmacologic effects of harringtonine on human leukemia-lymphoma cells. Cancer Chemother Pharmacol 1985; 14: 206-210
    PubMedSearch in Google Scholar
  • 4 Liu YP, Ueda T, Yoshida A, Iwasaki H, Nakamura T. Effect of harringtonine on apoptotic cell death and cell cycle progression in human leukemia HL60 cells. Anticancer Res 1994; 14: 1509-1516
    PubMedSearch in Google Scholar
  • 5 Han J. Traditional Chinese medicine and the search for new antineoplastic drugs. J Ethnopharmacol 1988; 24: 1-17
    CrossrefPubMedSearch in Google Scholar
  • 6 Takeda S, Yajima N, Kitazato K, Unemi N. Antitumor activities of harringtonine and homoharringtonine, Cephalotaxus alkaloids which are active principles from plant by intraperitoneal and oral administration. J Pharmacobiodyn 1982; 10: 841-847
    PubMedSearch in Google Scholar
  • 7 Paudler WW, Kerley GI, McKay J. The alkaloids of Cephalotaxus drupacea and Cephalotaxus fortunei . J Org Chem 1963; 28: 2194-2197
    CrossrefPubMedSearch in Google Scholar
  • 8 Powell RG, Weisleder D, Smith jr. CR, Rohwedder WK. Structures of harringtonine, isoharringtonine, and homoharringtonine. Tetrahedron Lett 1970; 11: 815-818
    CrossrefPubMedSearch in Google Scholar
  • 9 Quintas-Cardama A, Kantarjian H, Cortes J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer 2009; 115: 5382-5393
    CrossrefPubMedSearch in Google Scholar
  • 10 Chen Y, Li S. Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia. Onco Target Ther 2014; 7: 177-186
    PubMedSearch in Google Scholar
  • 11 Zhang W, Bai XF, Bu ZS, Wang JM, Yu XJ, Yuan Q. Enhanced production of harringtonine and homoharringtonine in Cephalotaxus fortunei callus culture by periodic temperature oscillation. Biotechnol Lett 1998; 20: 63-66
    CrossrefPubMedSearch in Google Scholar
  • 12 Li YC, Jiang XX, Long XJ. Effects and action mechanisms of sodium fluoride (NaF) on the growth and cephalotaxine production of Cephalotaxus mannii suspension cells. Enzyme Microb Tech 2014; 67: 77-81
    CrossrefPubMedSearch in Google Scholar
  • 13 Li YC. Enhanced cephalotaxine production in Cephalotaxus mannii suspension cultures by combining glycometabolic regulation and elicitation. Process Biochem 2014; 49: 2279-2284
    CrossrefPubMedSearch in Google Scholar
  • 14 Li W, Deng YL, Dai RJ, Yu YH, Saeed MK, Li LN, Meng WW, Zhang XS. Chromatographic fingerprint analysis of Cephalotaxus sinensis from various sources by high-performance liquid chromatography-diodearray detection-electrospray ionization-tandem mass spectrometry. J Pharm Biomed Anal 2007; 45: 38-46
    CrossrefPubMedSearch in Google Scholar
  • 15 Moirangthem DS, Borah JC, Laishram S, Kalita MC, Talukdar NC. HPLC analysis of harringtonine and homoharringtonine in the needles of Cephalotaxus griffithii alkaloid fraction and cytotoxic activity on chronic myelogenous leukaemia K562 cell. Nat Prod Res 2014; 28: 1503-1506
    CrossrefPubMedSearch in Google Scholar
  • 16 Liu ZH, Du QZ, Wang KW, Xiu LL, Song GL. Completed preparative separation of alkaloids from Cephaltaxus fortunine by step-pH-gradient high-speed counter-current chromatography. J Chromatogr A 2009; 1216: 4663-4667
    CrossrefPubMedSearch in Google Scholar
  • 17 Sakamoto S, Miyamoto T, Usui K, Tanaka H, Morimoto S. Sodium-periodate mediated harringtonine derivatives and their antiproliferative activity against HL-60 acute leukemia cells. J Nat Prod 2018; 81: 34-40
    CrossrefPubMedSearch in Google Scholar
  • 18 Sakamoto S, Yusakul G, Nuntawong P, Kitisripanya T, Putalun W, Miyamoto T, Tanaka H, Morimoto S. Development of an indirect competitive immunochromatographic strip test for rapid detection and determination of anticancer drug, harringtonine. J Chromatogr B Analyt Technol Biomed Life Sci 2017; 1048: 150-154
    CrossrefPubMedSearch in Google Scholar
  • 19 Sakamoto S, Yusakul G, Tsuneura Y, Putalun W, Usui K, Miyamoto T, Tanaka H, Morimoto S. Sodium periodate-mediated conjugation of harringtonine enabling the production of a highly specific monoclonal antibody, and the development of a sensitive quantitative analysis method. Analyst 2017; 142: 1140-1148
    CrossrefPubMedSearch in Google Scholar
  • 20 Erlanger BF. The preparation of antigenic hapten-carrier conjugates: a survey. Methods Enzymol 1980; 70: 85-104
    PubMedSearch in Google Scholar
  • 21 Sakamoto S, Nagamitsu R, Yusakul G, Miyamoto T, Tanaka H, Morimoto S. Ultrasensitive immunoassay for monocrotaline using monoclonal antibody produced by N,N -carbonyldiimidazole mediated hapten-carrier protein conjugates. Talanta 2017; 168: 67-72
    CrossrefPubMedSearch in Google Scholar
  • 22 Sakamoto S, Kohno T, Shimizu K, Tanaka H, Morimoto S. Detection of ganoderic acid A in Ganoderma lingzhi by an indirect competitive enzyme-linked immunosorbent assay. Planta Med 2016; 82: 747-751
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Pongkitwitoon B, Sakamoto S, Tanaka H, Tsuchihashi R, Kinjo J, Morimoto S, Putalun W. Development of an enzyme-linked immunosorbent assay to determine puerarin and its aglycone daidzein. J Nat Med 2011; 65: 31-36
    CrossrefPubMedSearch in Google Scholar
  • 24 Tothiam C, Phrompittayarat W, Putalun W, Tanaka H, Sakamoto S, Khan AI, Ingkaninan K. An enzyme-linked immunosorbant assay using monoclonal antibody against Bacoside A3 for determination of jujubogenin glycosides in Bacopa monnieri (L.) Wettst. Phytochem Anal 2011; 22: 385-391
    CrossrefPubMedSearch in Google Scholar
  • 25 Sakamoto S, Yusakul G, Pongkitwitoon B, Paudel MK, Tanaka H, Morimoto S. Simultaneous determination of soy isoflavone glycosides, daidzin and genistin by monoclonal antibody-based highly sensitive indirect competitive enzyme-linked immunosorbent assay. Food Chem 2015; 169: 127-133
    CrossrefPubMedSearch in Google Scholar
  • 26 Xuan LJ, Tanaka H, Morimoto S, Shoyama Y, Akanuma H, Muraoka K. Determination of 1,5-anhydro-glucitol-carrier protein conjugates by matrix-assisted laser desorption/ionization tof mass spectrometry and antibody formation. Spectroscopy 2000; 14: 85-92
    CrossrefPubMedSearch in Google Scholar
  • 27 Weiler EW, Zenk MH. Radioimmunoassay for determination of digoxin and related compounds in Digitalis lanata . Phytochemistry 1976; 15: 1537-1545
    CrossrefPubMedSearch in Google Scholar