Ceratamines, structurally simple microtubule-stabilizing antimitotic agents with unusual cellular effects.

doi:10.1158/0008-5472.CAN-04-4369

Paper

Ceratamines, structurally simple microtubule-stabilizing antimitotic agents with unusual cellular effects.

Published Apr 15, 2005 · G. Karjala, Q. Chan, E. Manzo

Cancer research

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33

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0

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Abstract

Ceratamine A and ceratamine B are heterocyclic alkaloids recently identified in a screen for compounds that arrest cells in mitosis. Treatment of breast carcinoma MCF-7 cells causes a concentration-dependent block of cell cycle progression exclusively at mitosis. In vitro studies with purified tubulin indicate that the ceratamines directly stimulate microtubule polymerization in the absence of microtubule-associated proteins. Cells treated with ceratamines show a dense perinuclear microtubule network in interphase and multiple pillar-like tubulin structures in mitotic cells. The ceratamines do not compete with paclitaxel for binding to microtubules in vitro. Unlike other microtubule-stabilizing agents, the ceratamines have simple structures with no chiral centers, making them attractive drug leads.

Study Snapshot

Ceratamines, structurally simple microtubule-stabilizing antimitotic agents, effectively block cell cycle progression in breast carcinoma MCF-7 cells, making them attractive drug leads.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Ceratamines, structurally simple microtubule-stabilizing antimitotic agents with unusual cellular effects.

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References

Peloruside A Does Not Bind to the Taxoid Site on β-Tubulin and Retains Its Activity in Multidrug-Resistant Cell Lines

Peloruside A, a microtubule-stabilizing agent from a marine sponge, is less susceptible to multidrug resistance and does not affect the taxoid binding site on -tubulin, maintaining its activity in multidrug-resistant cell lines.

Microtubules as a target for anticancer drugs

Microtubule-targeted drugs effectively suppress microtubule dynamics, leading to mitotic block and apoptosis, while some can also act as vascular-targeting agents to shut down tumor blood supply.

Ceratamines A and B, antimitotic heterocyclic alkaloids isolated from the marine sponge Pseudoceratina sp. collected in Papua New Guinea.

Ceratamines A and B show potential as antimitotic agents in marine sponges, with their structures elucidated by spectroscopic data.

The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity.

Laulimalide, a microtubule stabilizing agent, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity.

G2 DNA Damage Checkpoint Inhibition and Antimitotic Activity of 13-Hydroxy-15-oxozoapatlin*

13-hydroxy-15-oxozoapatlin (OZ) from the African tree Parinari curatellifolia is a G2 checkpoint inhibitor and antimitotic agent, potentially increasing the effectiveness of DNA-damaging therapies against cancers lacking p53 function.

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