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

AbstractA search for cytotoxic cholestane glycosides fromOrnithogalum saundersiae bulbs resulted in the isolation of three new OSW-1 analogues (1–3), a new cholestane bisdesmoside (4), a 5 β-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 of1–9 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 cytochromec 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.
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research