1. The flavonoid quercetin transiently inhibits the activity of taxol and nocodazole through interference with the cell cycle.
- Author
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Samuel T, Fadlalla K, Turner T, and Yehualaeshet TE
- Subjects
- Cell Adhesion, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Cyclin B1 metabolism, Food-Drug Interactions, G2 Phase drug effects, Humans, Microtubules drug effects, Neoplasms metabolism, Neoplasms pathology, Neoplasms prevention & control, Nocodazole pharmacology, Osmolar Concentration, Paclitaxel pharmacology, Time Factors, Tubulin metabolism, Tubulin Modulators pharmacology, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Antineoplastic Agents, Phytogenic metabolism, Cell Cycle drug effects, Neoplasms drug therapy, Nocodazole antagonists & inhibitors, Paclitaxel antagonists & inhibitors, Quercetin metabolism, Tubulin Modulators antagonists & inhibitors
- Abstract
Quercetin is a flavonoid with anticancer properties. In this study, we examined the effects of quercetin on cell cycle, viability, and proliferation of cancer cells, either singly or in combination with the microtubule-targeting drugs taxol and nocodazole. Although quercetin induced cell death in a dose-dependent manner, 12.5-50 μM quercetin inhibited the activity of both taxol and nocodazole to induce G2/M arrest in various cell lines. Quercetin also partially restored drug-induced loss in viability of treated cells for up to 72 h. This antagonism of microtubule-targeting drugs was accompanied by a delay in cell cycle progression and inhibition of the buildup of cyclin-B1 at the microtubule organizing center of treated cells. However, quercetin did not inhibit the microtubule targeting of taxol or nocodazole. Despite the short-term protection of cells by quercetin, colony formation and clonogenicity of HCT116 cells were still suppressed by quercetin or quercetin-taxol combination. The status of cell adherence to growth matrix was critical in determining the sensitivity of HCT116 cells to quercetin. We conclude that although long-term exposure of cancer cells to quercetin may prevent cell proliferation and survival, the interference of quercetin with cell cycle progression diminishes the efficacy of microtubule-targeting drugs to arrest cells at G2/M.
- Published
- 2010
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