Journal article
OSW-1: a natural compound with potent anticancer activity and a novel mechanism of action
JNCI : Journal of the National Cancer Institute, Vol.97(23), pp.1781-1785
12/07/2005
DOI: 10.1093/jnci/dji404
PMID: 16333034
Abstract
The naturally occurring compound 3beta,16beta,17alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1-->3)-(2-O-acetyl-alpha-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.
Details
- Title: Subtitle
- OSW-1: a natural compound with potent anticancer activity and a novel mechanism of action
- Creators
- Yan Zhou - The University of Texas MD Anderson Cancer CenterCelia Garcia-Prieto - Centre for Health Equity StudiesDennis A Carney - The University of Texas Health Science Center at HoustonRui-hua Xu - Medical OncologyHelene Pelicano - Center for Translational Molecular MedicineYing Kang - University of IowaWensheng Yu - University of IowaChanggang Lou - The University of Texas Health Science Center at HoustonSeiji Kondo - The University of Texas Health Science Center at HoustonJinsong LiuDavid M Harris - The University of Texas Health Science Center at HoustonZeev EstrovMichael J Keating - The University of Texas Health Science Center at HoustonZhendong Jin - University of IowaPeng Huang - Center for Translational Molecular Medicine
- Resource Type
- Journal article
- Publication Details
- JNCI : Journal of the National Cancer Institute, Vol.97(23), pp.1781-1785
- DOI
- 10.1093/jnci/dji404
- PMID
- 16333034
- ISSN
- 0027-8874
- eISSN
- 1460-2105
- Grant note
- CA16672 / NCI NIH HHS CA109041 / NCI NIH HHS CA85563 / NCI NIH HHS CA105073 / NCI NIH HHS
- Language
- English
- Date published
- 12/07/2005
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984366032302771
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