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- Title
OSW-1: a Natural Compound With Potent Anticancer Activity and a Novel Mechanism of Action.
- Authors
Yan Zhou; Garcia-Prieto, Celia; Carney, Dennis A.; Rui-Hua Xu; Pelicano, Helene; Ying Kang; Wensheng Yu; Changgang Lou; Seiji Kondo; Jinsong Liu; Harris, David M.; Estrov, Zeev; Keating, Michael F.; Zhendong Fin; Peng Huang
- Abstract
The naturally occurring compound 3β,16β,17α-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-β-D-xylopyranosyl)-(1↵3)-(2-O-acetyl-α-L-arabinopyranoside) (OSW-1) is found in the bulbs of Ornithogalum saudersiae and is highly cytotoxic against tumor cell lines. Using various human cancer and nonmalignant cell lines, we investigated the anticancer activity and selectivity of OSW-1 and its underlying mechanisms of action. OSW-1 exhibited extremely potent cytotoxic activity against cancer cells in vitro. Nonmalignant cells were statistically significantly less sensitive to OSW-1 than cancer cells, with concentrations that cause a 50% loss of cell viability 40–150-fold greater than those observed in malignant cells. Electron microscopy and biochemical analyses revealed that OSW-1 damaged the mitochondrial membrane and cristae in both human leukemia and pancreatic cancer cells, leading to the loss of transmembrane potential, increase of cytosolic calcium, and activation of calcium-dependent apoptosis. Clones of leukemia cells with mitochondrial DNA defects and respiration deficiency that had adapted the ability to survive in culture without mitochondrial respiration also were resistant to OSW-1. In vitro analysis revealed that OSW-1 effectively killed primary leukemia cells from chronic lymphocytic leukemia patients with disease refractory to fludarabine. The promising anticancer activity of OSW-1 and its unique mechanism of action make this compound worthy of further investigation for its potential to overcome drug resistance.
- Subjects
CELL lines; CELL culture; CANCER cells; MITOCHONDRIAL membranes; DRUG activation; ANTINEOPLASTIC agents; CANCER treatment
- Publication
JNCI: Journal of the National Cancer Institute, 2005, Vol 97, Issue 23, p1781
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/dji404