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

Guo, Xihan; Ni, Juan; Dai, Xueqin; Zhou, Tao; Yang, Guofang; Xue, Jinglun; Wang, Xu

doi:10.1016/j.mrgentox.2017.11.004

Cited by 24 publications

(17 citation statements)

References 57 publications

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“…Recently, we found that geraniin induces excessive CIN in human colorectal cancer Colo205 and Colo320 cells in vitro [Guo et al ], suggesting geraniin may undermine the efficiency of SAC in colorectal cancer cells. Assessment of SAC activity and mitotic aberrations has been standardized previously in our lab [Guo and Wang ; Guo et al ; Guo et al ; Guo et al ]. In present study, we find that geraniin treatment causes human colorectal cancer HCT116 cells to decrease the expression of several core SAC kinases, thereby weakening the SAC activity.…”

Section: Introductionsupporting

confidence: 63%

Geraniin Differentially Modulates Chromosome Stability of Colon Cancer and Noncancerous Cells by Oppositely Regulating their Spindle Assembly Checkpoint

Guo

Dai

et al. 2018

Environ and Mol Mutagen

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Geraniin has been reported to specifically induce apoptosis in multiple human cancers, but the underlying mechanism is poorly defined. The spindle assembly checkpoint (SAC) is a surveillance system to ensure high‐fidelity chromosome segregation during mitosis. Weakening of SAC to enhance chromosome instability (CIN) can be therapeutic because very high levels of CIN are lethal. In this study, we have investigated the effects of geraniin on the SAC of colorectal cancer HCT116 cells and noncancerous colon epithelial CCD841 cells. We find that treatment of HCT116 cells with geraniin leads to dose‐dependent decrease of cell proliferation, colony formation, and anchorage‐independent growth. Geraniin is found to induce apoptosis in mitotic and postmitotic HCT116 cells. Furthermore, geraniin weakens the SAC function of HCT116 cells by decreasing the transcriptional expression of several SAC kinases (particularly Mad2 and Bub1), which in turn leads to premature anaphase entry, mitotic aberrations, and CIN in HCT116 cells. In contrast, the proliferation of CCD841 cells is slightly inhibited by geraniin. Even more interestingly, geraniin increases the transcriptional expression of several SAC kinases (e.g., Mad1 and BubR1) to strengthen SAC efficiency, which contributes to the reduction of mitotic aberrations and CIN in CCD841 cells. Altogether, our findings reveal that the SAC pathway in human colon cancer and noncancerous cell lineages responses oppositely to geraniin treatment, resulting CIN promotion and suppression, respectively. Specific abrogation of SAC to induce catastrophic CIN in HCT116 cells may account for the selective anticancer action of geraniin.. Environ. Mol. Mutagen. 60:254–268, 2019. © 2018 Wiley Periodicals, Inc.

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Section: Introductionsupporting

confidence: 63%

Geraniin Differentially Modulates Chromosome Stability of Colon Cancer and Noncancerous Cells by Oppositely Regulating their Spindle Assembly Checkpoint

Guo

Dai

et al. 2018

Environ and Mol Mutagen

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“…Guo et al [54] reported that RES biphasically modulated chromosomal instability (CIN) in human normal colon epithelial cells. At low RES concentrations (0.1-1 µM) basal levels of CIN markers micronuclei (MN) and nucleoplasmic bridge (NPB) were reduced by 17-63%; the most marked decrease was noted at 0.1 µM.…”

Section: Resveratrolmentioning

confidence: 99%

“…Consistently with the above findings, cell viability was slightly increased (10%) and significantly decreased (35%) when incubated with 0.1 and 100 µM of RES. The authors suggested that the biphasic effect of RES on CIN might be attributed to the regulation of mitotic fidelity through the SAC (spindle assembly checkpoint) pathway which is a major cell-cycle regulatory network controlling chromosome segregation during mitosis [54].…”

Section: Resveratrolmentioning

confidence: 99%

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Jodynis‐Liebert

Kujawska

2020

JCM

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Many phytochemicals demonstrate nonmonotonic dose/concentration-response termed biphasic dose-response and are considered to be hormetic compounds, i.e., they induce biologically opposite effects at different doses. In numerous articles the hormetic nature of phytochemicals is declared, however, no experimental evidence is provided. Our aim was to present the overview of the reports in which phytochemical-induced biphasic dose-response is experimentally proven. Hence, we included in the current review only articles in which the reversal of response between low and high doses/concentrations of phytochemicals for a single endpoint was documented. The majority of data on biphasic dose-response have been found for phytoestrogens; other reports described these types of effects for resveratrol, sulforaphane, and natural compounds from various chemical classes such as isoquinoline alkaloid berberine, polyacetylenes falcarinol and falcarindiol, prenylated pterocarpan glyceollin1, naphthoquinones plumbagin and naphazarin, and panaxatriol saponins. The prevailing part of the studies presented in the current review was performed on cell cultures. The most common endpoint tested was a proliferation of tumor and non-cancerous cells. Very few experiments demonstrating biphasic dose-response induced by phytochemicals were carried out on animal models. Data on the biphasic dose-response of various endpoints to phytochemicals may have a potential therapeutic or preventive implication.

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“…However, in this study, PO-MSC viability decreased when resveratrol dose was above 10 μM. It seems that the osteogenic effect of resveratrol varies according to dosage or cell types (33)(34)(35)(36)(37). Therefore, further investigation on the optimal dosage and administration method of resveratrol for accelerating osteogenesis of PO-MSC is needed.…”

Section: Discussionmentioning

confidence: 63%

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

Moon

Kim

Lee

et al. 2020

Preprint

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Background: Osteoporosis is a metabolic bone disorder that leads to low bone mass and microstructural deterioration of bone tissue and increases bone fractures. Resveratrol, a natural polyphenol compound, has pleiotropic effects including anti-oxidative, anti-aging, and anti-cancer effects. Resveratrol also has roles in increasing osteogenesis and in up-regulating mitochondrial biogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, it is still unclear that resveratrol can enhance osteogenic differentiation or mitochondrial biogenesis of periosteum-derived MSCs (PO-MSCs), which play key roles in bone tissue maintenance and fracture healing. Thus, in order to test a possible preventive or therapeutic effect of resveratrol on osteoporosis, this study investigated effects of resveratrol treatments on osteogenic differentiation and mitochondrial biogenesis of PO-MSCs.Methods: The optimal doses of resveratrol treatment on PO-MSCs were determined by cell proliferation and viability assays. Osteogenic differentiation of PO-MSCs under resveratrol treatment was assessed by alkaline phosphatase activities (ALP, an early biomarker of osteogenesis) as well as by extracellular calcium deposit levels (a late biomarker). Mitochondrial biogenesis during osteogenic differentiation of PO-MSCs was measured by quantifying both mitochondrial mass and mitochondrial DNA (mtDNA) contents.Results: Resveratrol treatments above 10 µM seem to have negative effects on cell proliferation and viability of PO-MSCs. Resveratrol treatment (at 5 µM) on PO-MSCs during osteogenic differentiation increased both ALP activities and calcium deposits compared to untreated control groups, demonstrating an enhancing effect of resveratrol on osteogenesis. In addition, resveratrol treatment (at 5 µM) during osteogenic differentiation of PO-MSCs increased both mitochondrial mass and mtDNA copy numbers, indicating that resveratrol can bolster mitochondrial biogenesis in the process of PO-MSC osteogenic differentiation.Conclusion: Taken together, the findings of this study describe roles of resveratrol in promoting osteogenesis and mitochondrial biogenesis of human PO-MSCs suggesting a possible application of resveratrol as a supplement for osteoporosis and/or osteoporotic fractures.

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

Cited by 24 publications

References 57 publications

Geraniin Differentially Modulates Chromosome Stability of Colon Cancer and Noncancerous Cells by Oppositely Regulating their Spindle Assembly Checkpoint

Geraniin Differentially Modulates Chromosome Stability of Colon Cancer and Noncancerous Cells by Oppositely Regulating their Spindle Assembly Checkpoint

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

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