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Limonoids isolated from the Fortunella crassifolia and the Citrus junos with their cell death-inducing activity on Adriamycin-treated cancer cell

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Abstract

From the fruits of Fortunella crassifolia and the peels of Citrus junos, two new limonoids, fortunellone and junosol were isolated together with three known compounds including nomilin. The chemical structures of the new compounds were elucidated based on chemical/physicochemical evidence. For fortunellone, the absolute configuration was established by comparison of experimental and predicted electronic circular dichroism (ECD) data. Fortunellon and nomilin significantly increased the number of dead cells on adriamycin (ADR)-treated human cervical cancer cells (HeLa). On the other hand, fortunellon and nomilin did not affects the number of dead cells alone. These results suggested that fortunellone and nomilin may have the potency as the chemotherapy enhancement agents.

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References

  1. Wang YW, Zeng WC, Xu PY, Lan YJ, Zhu RX, Zhong K, Huang YN, Gao H (2012) Chemical composition and antimicrobial activity of the essential oil of kumquat (Fortunella crassifolia swingle) peel. Int J Mol Sci 13:3382–3393

    Article  CAS  Google Scholar 

  2. Nagahama K, Eto N, Shimojo T, Kondoh T, Nakahara K, Sakakibara Y, Fukui K, Suiko M (2015) Effect of kumquat (Fortunella crassifolia) pericarp on natural killer cell activity in vitro and in vivo. Biosci Biotechnol Biochem 79:1327–1336

    Article  CAS  Google Scholar 

  3. Manners GD (2007) Citrus limonoids: analysis, bioactivity, and biomedical prospects. J Agric Food Chem 55:8285–8294

    Article  CAS  Google Scholar 

  4. Tian Q, Miller EG, Ahmad H, Tang L, Patil BS (2001) Differential inhibition of human cancer cell proliferation by citrus limonoids. Nutr Cancer 40:180–184

    Article  CAS  Google Scholar 

  5. Soares DG, Godin AM, Menezes RR, Nogueira RD, Brito AMS, Melo ISF, Coura GME, Souza DG, Amaral FA, Paulino TP, Coelho MM, Machado RR (2014) Anti-inflammatory and antinociceptive activities of azadirachtin in mice. Planta Med 80:630–636

    Article  CAS  Google Scholar 

  6. Poulose SM, Harris ED, Edward D, Patil BS (2005) Citrus limonoids induce apoptosis in human neuroblastoma cells and have radical scavenging activity. J Nutr 135:870–877

    Article  CAS  Google Scholar 

  7. Battinelli L, Menqoni F, Lichtner M, Mazzanti G, Saija A, Mastroianni CM, Vullo V (2003) Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear cells. Planta Med 69:910–913

    Article  CAS  Google Scholar 

  8. Matsumoto T, Koike M, Arai C, Kitagawa T, Inoue E, Imahori D, Watanabe T (2018) Chemical structures and antimutagenic effects of unusual oximes from the peels of Citrus limon. Phytochem lett 25:118–121

    Article  CAS  Google Scholar 

  9. Matsumoto T, Kitagawa T, Teo S, Anai Y, Ikeda R, Imahori D, Ahmad HSB, Watanabe T (2018) Structures and antimutagenic effects of onoceranoid-type triterpenoids from the leaves of Lansium domesticum. J Nat Prod 81:2187–2194

    Article  CAS  Google Scholar 

  10. Matsumoto T, Imahori D, Saito Y, Zhang W, Ohta T, Yoshida T, Nakayama Y, Ashihara E, Watanabe T (2020) Cytotoxic activities of sesquiterpenoids from the aerial parts of Petasites japonicus against cancer stem cells. J Nat Med 74:689–701

    Article  CAS  Google Scholar 

  11. Matsumoto T, Imahori D, Achiwa K, Saito Y, Ohta T, Yoshida T, Kojima N, Yamashita M, Nakayama Y, Watanabe T (2020) Chemical structures and cytotoxic activities of the constituents isolated from Hibiscus tiliaceus. Fitoterapia 142:104524

    Article  CAS  Google Scholar 

  12. Damiani RM, Moura DJ, Viau CM, Caceres RA, Henriques JAP, Saffi J (2016) Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone. Arch Toxicol 90:2063–2076

    Article  CAS  Google Scholar 

  13. Cheung KG, Cole LK, Xiang B, Chen K, Ma X, Myal Y, Hatch GM, Tong Q, Dolinsky VW (2015) Sirtuin-3 (SIRT3) protein attenuates doxorubicin-induced oxidative stress and improves mitochondrial respiration in H9c2 cardiomyocytes. J Biol Chem 290:10981–10993

    Article  CAS  Google Scholar 

  14. Arnott S, Davie AW, Robertson JM, Sim GA, Watson DG (1961) The structure of limonin. X-ray analysis of epilimonol iodoacetate. J Chem Soc 4183–4200

  15. Bennett RD, Hasegawa S (1981) Limonoids of calamondin seeds. Tetrahedron 37:17–24

    Article  CAS  Google Scholar 

  16. Ruberto G, Renda A, Tringali C, Napoli EM, Simmonds MSJ (2002) Citrus limonoids and their semisynthetic derivatives as antifeedant agents against Spodoptera frugiperda larvae. A structure-activity relationship study. J Agric Food Chem 50:6766–6774

    Article  CAS  Google Scholar 

  17. Matsumoto T, Kitagawa T, Ohta T, Yoshida T, Imahori D, Teo S, Ahmad HSB, Watanabe T (2019) Structures of triterpenoids from the leaves of Lansium domesticum. J Nat Med 73:727–734

    Article  CAS  Google Scholar 

  18. Yamane T, Saito Y, Teshima H, Hagino M, Kakihana A, Sato S, Shimada M, Kato Y, Kuga T, Yamagishi N, Nakayama Y (2019) Hsp105α suppresses adriamycin-induced cell death via nuclear localization signal-dependent nuclear accumulation. J Cell Biochem 120:17951–17962

    Article  CAS  Google Scholar 

  19. Xu W, Xie S, Chen X, Pan S, Qian H, Zhu X (2021) Effects of quercetin on the efficacy of various chemotherapeutic drugs in cervical cancer cells. Drug Des Dev Ther 15:577–588

    Article  Google Scholar 

  20. Yang Q, Li S, Fu Z, Lin B, Zhou Z, Wang Z, Hua Y, Cai Z (2017) Shikonin promotes adriamycin-induced apoptosis by upregulating caspase-3 and caspase-8 in osteosarcoma. Mol Med Rep 16:1347–1352

    Article  CAS  Google Scholar 

  21. Spartan’10. Wavefunction Inc., Irvine, CA

  22. Gaussian 09, Revision D.01, Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski, JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian, Inc., Wallingford, CT

  23. Bruhn T, Schaumlöffel A, Hemberger Y, Pecitelli G (2013) SpecDis: quantifying the comparison of calculated and experimental electronic circular dichroism spectra. Chirality 25:243–249

    Article  CAS  Google Scholar 

  24. Nakayama Y, Saito Y, Soeda S, Iwamoto E, Ogawa S, Yamagishi N, Kuga T, Yamaguchi N (2014) Genistein induces cytokinesis failure through RhoA delocalization and anaphase chromosome bridging. J Cell Biochem 115:763–771

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Numbers 20H03397 and 20J14567.

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Authors and Affiliations

  1. Department of Public Health, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, 607-8412, Japan

    Takahiro Kitagawa, Takahiro Matsumoto, Daisuke Imahori, Mayuka Kobayashi, Masaya Okayama & Tetsushi Watanabe

  2. Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki, 859-3298, Japan

    Tomoe Ohta & Tatsusada Yoshida

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  1. Takahiro Kitagawa
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  2. Takahiro Matsumoto
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  4. Mayuka Kobayashi
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  7. Tatsusada Yoshida
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  8. Tetsushi Watanabe
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Correspondence to Takahiro Matsumoto or Tetsushi Watanabe.

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11418_2021_1528_MOESM1_ESM.docx

Supplementary file1. Experimental details; the 1D and 2D NMR spectra for the new compounds, the DFT-optimized structures of conformers of 1 with its equilibrium population, and the experimental ECD spectra of 3 and 4 are available free of charge via the Internet. (DOCX 21232 kb)

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Kitagawa, T., Matsumoto, T., Imahori, D. et al. Limonoids isolated from the Fortunella crassifolia and the Citrus junos with their cell death-inducing activity on Adriamycin-treated cancer cell. J Nat Med 75, 998–1004 (2021). https://doi.org/10.1007/s11418-021-01528-8

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  • DOI: https://doi.org/10.1007/s11418-021-01528-8

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