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 (2–6) 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.
Data availability
The data that support the findings of this study are available from the corresponding authors upon reasonable request.
References
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Kai H, Baba M, Okuyama T (2007) Two new megastigmanes from the leaves of Cucumis sativus. Chem Pharm Bull 55:133–136
Kimura J, Maki N (2002) New loliolide derivatives from the brown alga Undaria pinnatifida. J Nat Prod 65:57–58
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
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
Wu GS (2009) TRAIL as a target in anti-cancer therapy. Cancer Lett 285:1–5
Amarante-Mendes GP, Griffith TS (2015) Therapeutic applications of TRAIL receptor agonists in cancer and beyond. Pharmacol Ther 155:117–131
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
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
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
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
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
Lindhagen E, Nygren P, Larsson R (2008) The fluorometric microculture cytotoxicity assay. Nat Protoc 3:1364–1369
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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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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DOI: https://doi.org/10.1007/s11418-022-01670-x