The flavonoid quercetin transiently inhibits the activity of taxol and nocodazole through interference with the cell cycle.
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.
Pathobiology Department, Tuskegee University, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee, Alabama 36088, USA. tsamuel@tuskegee.edu
Temesgen
T
Samuel
Khalda
K
Fadlalla
Timothy
T
Turner
Teshome E
TE
Yehualaeshet
D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D002448:Cell Adhesion; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism; D018565:Food-Drug Interactions; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015739:Nocodazole / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009994:Osmolar Concentration; D017239:Paclitaxel / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011794:Quercetin / Q000378:metabolism*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; C534699:CCNB1 protein, human; D056744:Cyclin B1; D014404:Tubulin; D050257:Tubulin Modulators; D016159:Tumor Suppressor Protein p53; D011794:Quercetin; D017239:Paclitaxel; D015739:Nocodazole