Journal of Natural Medicines

, Volume 73, Issue 1, pp 131–145 | Cite as

Cholestane glycosides from Ornithogalum saundersiae bulbs and the induction of apoptosis in HL-60 cells by OSW-1 through a mitochondrial-independent signaling pathway

  • Tomoki Iguchi
  • Minpei KurodaEmail author
  • Rei Naito
  • Tomoyuki Watanabe
  • Yukiko Matsuo
  • Akihito Yokosuka
  • Yoshihiro Mimaki
Original Paper


A search for cytotoxic cholestane glycosides from Ornithogalum saundersiae bulbs resulted in the isolation of three new OSW-1 analogues (13), a new cholestane bisdesmoside (4), a 5β-cholestane diglycoside (5), and four new 24(23 → 22)-abeo-cholestane glycosides (69), together with 11 known cholestane glycosides (1020), including OSW-1 (11). The structures of 19 were determined based on conventional spectroscopic analysis and chemical evidence. As expected, based on previous data, 13 exhibited potent cytotoxic activity against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells. Furthermore, the ability of OSW-1 to induce apoptosis in HL-60 cells was examined. Aggregation of nuclear chromatin, accumulation of the sub-G1 cells, DNA fragmentation, and caspase-3 activation were assessed in HL-60 cells treated with OSW-1, providing evidence for OSW-1-induced apoptosis in HL-60 cells. No mitochondrial membrane potential or release of cytochrome c into the cytoplasm were observed in the OSW-1-treated apoptotic HL-60 cells, indicating that a mitochondria-independent signaling pathway is involved in apoptotic cell death.


Ornithogalum saundersiae Cholestane glycosides OSW-1 Cytotoxity HL-60 cells Apoptosis 

Supplementary material

11418_2018_1252_MOESM1_ESM.doc (875 kb)
Supplementary material 1 (DOC 875 kb)


  1. 1.
    Kubo S, Mimaki Y, Sashida Y, Nikaido T, Ohmoto T (1992) Acylated cholestane glycosides from the bulbs of Ornithogalum saundersiae. Phytochemistry 31:3969–3973CrossRefGoogle Scholar
  2. 2.
    Mimaki Y, Kuroda M, Kameyama A, Sashida Y, Hirano T, Oka K, Maekawa R, Wada T, Sugita K, Beutler JA (1997) Cholestane glycosides with potent cytostatic activities on various tumor cells from Ornithogalum saundersiae bulbs. Bioorganic Med Chem Lett 7:633–636CrossRefGoogle Scholar
  3. 3.
    Iguchi T, Kuroda M, Naito R, Watanabe T, Matsuo Y, Yokosuka A, Mimaki Y (2017) Structural characterization of cholestane rhamnosides from Ornithogalum saundersiae bulbs and their cytotoxic activity against cultured tumor cells. Molecules 22:1243–1263CrossRefGoogle Scholar
  4. 4.
    Kuroda M, Mimaki Y, Yokosuka A, Sashida Y (2001) Cholestane glycosides from the bulbs of Galtonia candicans and their cytotoxicity. Chem Pharm Bull 49:1042–1046CrossRefGoogle Scholar
  5. 5.
    Mimaki Y, Kuroda M, Kameyama A, Sashida Y, Hirano T, Oka K, Koike K, Nikaido T (1996) A new cytotoxic cholestane bisdesmoside from Ornithogalum saundersiae bulbs. Biosci Biotech Biochem 60:1049–1050CrossRefGoogle Scholar
  6. 6.
    Sashida Y, Oka K, Hirano T, Mimaki Y, Kuroda M, Fujii A, Miyata Y (1997) Steroidal glycosides and Pharmaceutical products containing them as active ingredients. Patent No. JP1997-48795Google Scholar
  7. 7.
    Kuroda M, Mimaki Y, Sashida Y, Hirano T, Oka K, Dobashi A (1995) A novel 16,23-epoxy-5beta-cholestane glycoside with potent inhibitory activity on proliferation of human peripheral blood lymphocytes from Ornithogalum saundersiae bulbs. Chem Pharm Bull 43:1257–1259CrossRefGoogle Scholar
  8. 8.
    Mimaki Y, Kuroda M, Sashida Y, Hirano T, Oka K, Dobashi A (1996) Three novel rearranged cholestane glycosides from Ornithogalum saundersiae bulbs and their cytostatic activities on leukemia HL-60 and MOLT-4 cells. Tetrahedron Lett 37:1245–1248CrossRefGoogle Scholar
  9. 9.
    Kuroda M, Mimaki Y, Sashida Y (1999) Saundersiosides C-H, rearranged cholestane glycosides from the bulbs of Ornithogalum saundersiae and their cytostatic activity on HL-60 cells. Phytochemistry 52:435–443CrossRefGoogle Scholar
  10. 10.
    Pingping T, Biao Y (2009) Total synthesis of candicanoside A, a rearranged cholestane disaccharide, and its 4′′-O-(p-methoxybenzoate) congener. Eur J Org Chem 2009(2):259–269CrossRefGoogle Scholar
  11. 11.
    Garcia-Prieto C, Riaz Ahmed KB, Chen Z, Zhou Y, Hammoudi N, Kang Y, Lou C, Mei Y, Jin Z, Huang P (2013) Effective killing of leukemia cells by the natural product OSW-1 through disruption of cellular calcium homeostasis. J Biol Chem 288:3240–3250CrossRefGoogle Scholar
  12. 12.
    Yokosuka A, Jitsuno M, Yui S, Yamazaki M, Mimaki Y (2009) Steroidal glycosides from Agave utahensis and their cytotoxic activity. J Nat Prod 72:1399–1404CrossRefGoogle Scholar
  13. 13.
    Yokosuka A, Suzuki T, Tatsuno S, Mimaki Y (2014) Steroidal glycosides from the underground parts of Yucca glauca and their cytotoxic activities. Phytochemistry 101:109–115CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Tomoki Iguchi
    • 1
  • Minpei Kuroda
    • 1
    Email author
  • Rei Naito
    • 1
  • Tomoyuki Watanabe
    • 1
  • Yukiko Matsuo
    • 1
  • Akihito Yokosuka
    • 1
  • Yoshihiro Mimaki
    • 1
  1. 1.Department of Medicinal Pharmacognosy, School of PharmacyTokyo University of Pharmacy and Life SciencesTokyoJapan

Personalised recommendations