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.
ACKNOWLEDGMENTS
We thank Tsegaye Habtemariam, Cesar Fermin, and Frederick Tippett for support through HRSA/COE D34HP00001-22-00; Sibyl Bowie for editorial assistance; John Williams for technical assistance at the Tuskegee University RCMI imaging core facility; John Heath, Clayton Yates, Starlette Sharp, and Patricia Adams for various technical support and advice. We thank Bert Vogelstein for HCT116 cells, John Reed for PPC1 cells, and Leslie Wilson for MCF7 cells. We acknowledge the research training support by the MSM/TU/UABCC Cancer Partnership to T. Samuel. This work was supported by NIH/NCI/NIGMS grant 1SC2CA138178 and U54 CA 118623. The authors have no conflict of interest to disclose.