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

Author:
Iguchi, Tomoki, Kuroda, Minpei, Naito, Rei, Watanabe, Tomoyuki, Matsuo, Yukiko, Yokosuka, Akihito, Mimaki, Yoshihiro
Source:
Natural medicines 2019 v.73 no.1 pp. 131-145
ISSN:
1340-3443
Subject:
DNA fragmentation, Ornithogalum saundersiae, apoptosis, bulbs, caspase-3, chromatin, cytochrome c, cytoplasm, cytotoxicity, desmosides, humans, lungs, membrane potential, mitochondrial membrane, neoplasm cells, signal transduction, spectral analysis
Abstract:
A search for cytotoxic cholestane glycosides from Ornithogalum saundersiae bulbs resulted in the isolation of three new OSW-1 analogues (1–3), a new cholestane bisdesmoside (4), a 5β-cholestane diglycoside (5), and four new 24(23 → 22)-abeo-cholestane glycosides (6–9), together with 11 known cholestane glycosides (10–20), including OSW-1 (11). The structures of 1–9 were determined based on conventional spectroscopic analysis and chemical evidence. As expected, based on previous data, 1–3 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.
Agid:
6275509