Biphasic regulation of spindle assembly checkpoint by low and high concentrations of resveratrol leads to the opposite effect on chromosomal instability

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2018-01, Vol.825, p.19-30
• Main Authors: Guo, Xihan, Ni, Juan, Dai, Xueqin, Zhou, Tao, Yang, Guofang, Xue, Jinglun, Wang, Xu
• Format: Article
• Language: English
• Subjects: Aurora Kinase B - genetics; Aurora Kinase C - genetics; Cell Cycle Proteins - genetics; Cell Line; Chromosomal Instability; Chromosomal Proteins, Non-Histone - genetics; Colon - cytology; Colon - drug effects; Colon - metabolism; Dose-Response Relationship, Drug; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene Expression Regulation - drug effects; Hormesis; Human colon cells; Humans; M Phase Cell Cycle Checkpoints - drug effects; Mitotic aberrations; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - genetics; Proto-Oncogene Proteins - genetics; Resveratrol; Resveratrol - toxicity; Spindle assembly checkpoint
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2017.11.004

[Display omitted] •A broad range of RSV doses (0.01–100μM) was analyzed.•RSV prevented spontaneous MN, NPB and NB at 0.1–1μM while inducing MN at 100μM.•Mitotic aberrations were prevented by 0.1μM RSV but promoted by 100μM RSV.•The SAC was sustained and overridden by 0.1 and 100μM RSV, respectively.•RSV displayed hormetic dose response to CIN through the biphasic regulation of SAC network. Resveratrol (RSV) is a naturally occurring polyphenolic phytoalexin possessing numerous health-promoting effects. Chromosomal instability (CIN), usually results from defective spindle assembly checkpoint (SAC), is a major contributor to many diseases. While it’s recently recognized that RSV exhibits a nonlinear dose response for disease prevention, whether it’s the case for its role in CIN remains unknown. Here, we investigated the potential of a broad range of RSV concentrations (0.01–100μM) on CIN and the underlying mechanisms in human normal colon epithelial NCM460 cells. CIN was measured by cytokinesis-block micronucleus assay; mitotic fidelity was determined by aberrant mitosis analysis; SAC activity was assessed by nocodazole-challenge assay, and the expression of SAC genes was examined by RT-qPCR. We found that 0.1μM RSV significantly reduced CIN (P