Abstract |
Lissoclinolide is a small non-nitrogenous lactone isolated from the marine ascidian Lissoclinum patella. Previous studies of lissoclinolide (isolated from a fungus and an actinomycete) have identified varying activity against both Gram-negative and Gram-positive bacteria. In this study, lissoclinolide was able to inhibit cell growth in various mammalian tumor lines at an average IC(50) of 395 nM (determined by MTT conversion after 48-h treatment). Treatment of HCT 116 human colon tumor cells with 2.4 microM lissoclinolide resulted in a strong arrest in the G(2)/M phase of the cell cycle after 24-h exposure. A daughter cell line lacking p53 showed an identical response while there was a slight increase in cytotoxicity towards a p21 null cell line. Although treatment with 2.4 microM lissoclinolide did not result in apoptosis after 48 h, this arrest was not reversible when drug wash out was attempted. The mechanism of action does not appear to involve tubulin, ubiquitin-specific isopeptidases, p53 or p21. COMPARE analysis in the NCI 60 cell line tumor panel revealed a moderate selectivity towards colon tumor cell lines.
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Authors | Adam D Richardson, Chris M Ireland |
Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 195
Issue 1
Pg. 55-61
(Feb 15 2004)
ISSN: 0041-008X [Print] United States |
PMID | 14962505
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- lissoclinolide
- 4-Butyrolactone
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Topics |
- 4-Butyrolactone
(analogs & derivatives, isolation & purification, pharmacology)
- Animals
- Antineoplastic Agents
(isolation & purification, pharmacology)
- Cell Division
(drug effects)
- Cell Survival
(drug effects)
- Colonic Neoplasms
(pathology)
- Drug Screening Assays, Antitumor
- HCT116 Cells
- Humans
- Inhibitory Concentration 50
- Urochordata
(chemistry)
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