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A new 1,2-diketone physalin isolated from Physalis minima and TRAIL-resistance overcoming activity of physalins

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Abstract

A new 1,2-diketone physalin, physalin XII (1), and 13 known compounds were isolated from the methanol extract of Physalis minima whole plant collected in Thailand. Among them, five physalins (26) had tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistance overcoming activity, and physalin F (3) was the most active with an IC50 value of 0.39 µM against human gastric adenocarcinoma cell line AGS in the presence of TRAIL (100 ng/mL). An investigation of the TRAIL-resistance overcoming activity of physalins using western blot analysis showed that 3 promoted TRAIL-induced apoptosis by suppressing anti-apoptotic proteins c-FLIP and Bcl-2.

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Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

References

  1. Matsuura T, Kawai M, Nakashima R, Butsugan Y (1970) Structures of physalin A and physalin B, 13,14-seco-16,24-cyclo-steroids from Physalis alkekengi var. Francheti J Chem Soc Perkin Trans 15:664–670

    Google Scholar 

  2. Wu J, Zhao J, Zhang T, Gu Y, Khan I, Zou Z, Xu Q (2021) Naturally occurring physalins from the genus Physalis: a review. Phytochemistry 191:112925

    Article  CAS  PubMed  Google Scholar 

  3. Yang YK, Xie SD, Xu WX, Nian Y, Liu XL, Peng XR, Ding ZT, Qiu MH (2016) Six new physalins from Physalis alkekengi var. franchetii and their cytotoxicity and antibacterial activity. Fitoterapia 112:144–152

    Article  CAS  PubMed  Google Scholar 

  4. Sun CP, Qiu CY, Zhao F, Kang N, Chen LX, Qiu F (2017) Physalins V-IX, 16,24-cyclo-13,14-seco withanolides from Physalis angulata and their antiproliferative and anti-inflammatory activities. Sci Rep 7:4057

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jacobo-Herrera NJ, Bremner P, Márquez N, Gupta MP, Gibbons S, Muñoz E, Heinrich M (2006) Physalins from Witheringia solanacea as modulators of the NF-κB cascade. J Nat Prod 69:328–331

    Article  CAS  PubMed  Google Scholar 

  6. Arai MA, Uchida K, Sadhu SK, Ahmed F, Ishibashi M (2014) Physalin H from Solanum nigrum as Hh signaling inhibitor blocks GLI1-DNA complex formation. Beil J Org Chem 10:134–140

    Article  Google Scholar 

  7. Hosoya T, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M (2008) Naturally occurring small-molecule inhibitors of Hedgehog/GLI-mediated transcription. ChemBioChem 9:1082–1092

    Article  CAS  PubMed  Google Scholar 

  8. Jitrangsri K, Takaya A, Hara Y, Sadhu SK, Ahmed F, Ishibashi M (2021) Bioactivity-guided isolation of TRAIL-resistance overcoming activity compounds from the leaves of Murraya exotica. Nat Prod Commun 16:1934578X211065843

    CAS  Google Scholar 

  9. Manome T, Hara Y, Ahmed F, Sadhu SK, Ishibashi M (2022) Thannilignan glucoside and 2-(β-glucopyranosyl)-3-isoxazolin-5-one derivative, two new compounds isolated from Terminalia bellirica. J Nat Med 76:482–489

    Article  CAS  PubMed  Google Scholar 

  10. von Karstedt S, Montinaro A, Walczak H (2017) Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy. Nat Rev Cancer 17:352–366

    Article  Google Scholar 

  11. Makino B, Kawai M, Iwata Y, Yamamura H, Butsugan Y, Ogawa K, Hayashi M (1995) Physalins possessing an endoperoxy structure from Physalis alkekengi var. francheti. structural revision of physalin K. Bull Chem Soc Jpn 68:219–226

    Article  CAS  Google Scholar 

  12. Kawai M, Makino B, Taga T, Miwa Y, Yamamoto T, Furuta T, Yamamura H, Butsugan Y, Ogawa K, Hayashi M (1994) Crystal structures of 5α,6α-epoxy and 2,3-dihydro derivatives of physalin B, a 13,14-seco-16,24-cyclosteroid, and their 1H NMR spectral analysis. Bull Chem Soc Jpn 67:222–226

    Article  CAS  Google Scholar 

  13. Choudhary MI, Samreen SY, Shah SAA, Ahmed S, Rahman A (2006) Biotransformation of physalin H and leishmanicidal activity of its transformed products. Chem Pharm Bull 54:927–930

    Article  CAS  Google Scholar 

  14. Makino B, Kawai M, Ogura T, Nakanishi M, Yamamura H, Butsugan Y (1995) Structural revision of physalin H isolated from Physalis angulata. J Nat Prod 58:1668–1674

    Article  CAS  Google Scholar 

  15. Row LR, Reddy KS, Sarma NS, Matsuura T, Nakashima R (1980) New physalins from Physalis angulata and Physalis lancifolia. Structure and reactions of physalins D, I G and K. Phytochemistry 19:1175–1181

    Article  CAS  Google Scholar 

  16. Januário AH, Filho ER, Pietro RCLR, Kashima S, Sato DN, França SC (2002) Antimycobacterial physalins from Physalis angulata L. (Solanaceae). Phytother Res 16:445–448

    Article  PubMed  Google Scholar 

  17. Catalán CAN, de Heluani CS, Kotowicz C, Gedris TE, Herz W (2003) A linear sesterterpene, two squalene derivatives and two peptide derivatives from Croton hieronymi. Phytochemistry 64:625–629

    Article  PubMed  Google Scholar 

  18. Kai H, Baba M, Okuyama T (2007) Two new megastigmanes from the leaves of Cucumis sativus. Chem Pharm Bull 55:133–136

    Article  CAS  Google Scholar 

  19. Kimura J, Maki N (2002) New loliolide derivatives from the brown alga Undaria pinnatifida. J Nat Prod 65:57–58

    Article  CAS  PubMed  Google Scholar 

  20. Hammami S, Jannet HB, Bergaoui A, Ciavatta L, Cimino G, Mighri Z (2004) Isolation and structure elucidation of a flavanone, a flavanone glycoside and vomifoliol from Echiochilon fruticosum growing in Tunisia. Molecules 9:602–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Piggott L, Omidvar N, Pérez SM, Eberl M, Clarkson RW (2011) Suppression of apoptosis inhibitor c-FLIP selectively eliminates breast cancer stem cell activity in response to the anti-cancer agent, TRAIL. Breast Cancer Res 13:2–15

    Article  Google Scholar 

  22. Wu GS (2009) TRAIL as a target in anti-cancer therapy. Cancer Lett 285:1–5

    Article  CAS  PubMed  Google Scholar 

  23. Amarante-Mendes GP, Griffith TS (2015) Therapeutic applications of TRAIL receptor agonists in cancer and beyond. Pharmacol Ther 155:117–131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Walczak H, Bouchon A, Stahl H, Krammer PH (2000) Tumor necrosis factor-related apoptosis-inducing ligand retains its apoptosis-inducing capacity on Bcl-2- or Bcl-xL-overexpressing chemotherapy-resistant tumor cells. Cancer Res 60:3051–3057

    CAS  PubMed  Google Scholar 

  25. Kump E, Ji J, Wernli M, Hausermann P, Erb P (2008) Gli2 upregulates cFlip and renders basal cell carcinoma cells resistant to death ligand-mediated apoptosis. Oncogene 27:3856–3864

    Article  CAS  PubMed  Google Scholar 

  26. Regl G, Kasper M, Schnidar H, Eichberger T, Neill GW, Philpott MP, Esterbauer H, Hauser-Kronberger C, Frischauf AM, Aberger F (2004) Activation of the BCL2 promoter in response to Hedgehog/GLI signal transduction is predominantly mediated by GLI2. Cancer Res 64:7724–7731

    Article  CAS  PubMed  Google Scholar 

  27. Zhang D, Liu J, Wang Y, Chen J, Chen T (2011) shRNA-mediated silencing of Gli2 gene inhibits proliferation and sensitizes human hepatocellular carcinoma cells towards TRAIL-induced apoptosis. J Cell Biochem 112:3140–3150

    Article  CAS  PubMed  Google Scholar 

  28. Zhang D, Li H, Lau W, Cao L, Li Y, Jiang X, Yang X, Xue P (2014) Gli2 silencing enhances TRAIL-induced apoptosis and reduces tumor growth in human hepatoma cells in vivo. Cancer Biol Ther 15:1667–1676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lindhagen E, Nygren P, Larsson R (2008) The fluorometric microculture cytotoxicity assay. Nat Protoc 3:1364–1369

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr. Takashi Koyano (Temko Corporation) and Prof. Thaworn Kowithayakorn (Khon Kaen University) for their collaboration in collecting and identifying plant materials. This work was supported by KAKENHI Grant Nos. 20H03394 and 20K16024 from the Japan Society for Promotion of Science.

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Correspondence to Yasumasa Hara or Masami Ishibashi.

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Manome, T., Hara, Y. & Ishibashi, M. A new 1,2-diketone physalin isolated from Physalis minima and TRAIL-resistance overcoming activity of physalins. J Nat Med 77, 370–378 (2023). https://doi.org/10.1007/s11418-022-01670-x

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