Geraniin suppresses ovarian cancer growth through inhibition of NF-κB activation and downregulation of Mcl-1 expression

Wang, Xue; Chen, Zhuo; Li, Xiao; Jiang, Zheng-kui; Zhao, Yanqiu; Ping, Fengfeng

doi:10.1002/jbt.21929

Cited by 22 publications

(18 citation statements)

References 23 publications

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“…Geraniin from Geranium thunbergii was reported to have chemopreventive effects . This compound was revealed to induce apoptotic responses in different cancer cells, including melanoma cells, breast cancer cells, and lung adenocarcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways

Yeh

Hsieh

Yang

et al. 2019

Environmental Toxicology

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Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti‐migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC‐9 and SCC‐14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase‐2 (MMP‐2) of oral cancer cells in a concentration‐dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal‐regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti‐migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC‐9 and SCC‐14 cells in vitro through a molecular mechanism that involves the attenuation of MMP‐2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways.

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Section: Discussionmentioning

confidence: 99%

Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways

Yeh

Hsieh

Yang

et al. 2019

Environmental Toxicology

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“…Geraniin has been found to inhibit proliferation and induce apoptosis in multiple human tumor cells [Lee et al ; Li et al ; Ko ; Zhai et al ; Ren et al ; Wang et al ; Wang et al ]. However, molecular mechanism underlying the antitumor effects of geraniin has not been fully evaluated.…”

Section: Disscussionmentioning

confidence: 99%

“…This means SAC is a more favorable therapeutic target because it is more critical for the survival of a cancer cell than a normal cell. Geraniin has been found to inhibit proliferation and induce apoptosis in multiple human tumor cells [Lee et al 2008;Li et al 2013;Ko 2015;Zhai et al 2016;Ren et al 2017;Wang et al 2017a;Wang et al 2017b]. However, molecular mechanism underlying the antitumor effects of geraniin has not been fully evaluated.…”

Section: Disscussionmentioning

confidence: 99%

“…The natural occurrence of geraniin has been verified in other ethnopharmacological important plants, such as a broad species of genus Geranium (e.g., G. sibiricum and G. thunbergii ), highlighting its role as an active ingredient in traditional medicines [Cheng et al ]. Recently, a large number of in vitro and in vivo experiments have reported that geraniin induces apoptosis in human glioma [Ren et al ], breast cancer [Zhai et al ], ovarian cancer [Wang et al ], lung cancer [Li et al ; Ko ], melanoma [Lee et al ], and osteosarcoma cells [Wang et al ], whereas leaving untransformed cells unaffected. This selectivity makes geraniin ideal for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

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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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“…MCL1 gene is one of those antiapoptotic members serving as a gateway protein that guards against apoptosis in OVC . Its overexpression in OVC has been reported and is linked to poor prognosis outcomes . We also interrogated the public databases and found that MCL1 gene predicted a significantly poor survival rate of patients with OVC.…”

Section: Introductionmentioning

confidence: 99%

miR‐153‐3p regulates progression of ovarian carcinoma in vitro and in vivo by targeting MCL1 gene

Cui

Zhang

Zhao

et al. 2019

J of Cellular Biochemistry

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The study of either miR‐153‐3p or MCL1 gene in ovarian carcinoma (OVC) has been reported; however, the interaction between miR‐153‐3p and MCL1 gene in OVC as well as the influence of their interaction on OVC progression has not been reported yet. Herein we intended to study the effects of miR‐153‐3p/MCL1 axis in OVC. Web‐based bioinformatics algorithms including DIANA TarBase 8.0, PicTar, and TargetScan Human 7.2 were used to predict the microRNAs (miRNAs) that could target MCL1 mRNA. Patient characteristics data collection and tissue sample immunohistochemical staining were used to determine the expression level of miR‐153‐3p and MCL1. We determined to unravel the effects of the pairing‐up of miR‐153‐3p and MCL1 mRNA in OVC cell lines (OVCAR3 cell line and A2780) and xenografts (immunodeficient(immunodeficient Rag−/− mice) using several methods including real‐time quantitative reverse transcription polymerase chain reaction, westernWestern blot, colony formation assay, wound healing assay, Transwell invasion assay, flow cytometry assay, and xenograft assay. These experiments were performed to study OVC cellular activities such as cell growth and death and so forth in vitro and in vivo. Plenty of miRNAs that can target MCL1 mRNA have been identified, and we have narrowed them down to miR‐153‐3p. MCL1 gene was found overexpressed in OVC tissues and OVC cell lines at RNA and protein levels, whereas miR‐153‐3p was found under‐expressed in OVC tissues and cells. miR‐153‐3p was found to target MCL1 mRNA and interfered OVC progression. The repression of MCL1 gene expression caused by either miR‐153‐3p or small interfering RNA technique led to significantly reduced OVC cell growth and invasion in vitro. Lastly, the engraftment of transfected human OVC cells into Rag−/− mice confirmed the in vitro results. MCL1 gene acts as a cancer facilitator in OVC. In this study, we revealed the role of miR‐153‐3p on OVC progression by targeting MCL1 gene. Our work could comprehend the current understanding of OVC progression and contribute to the underlying aggression mechanism of this cancer.

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Geraniin suppresses ovarian cancer growth through inhibition of NF-κB activation and downregulation of Mcl-1 expression

Cited by 22 publications

References 23 publications

Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways

Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways

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

miR‐153‐3p regulates progression of ovarian carcinoma in vitro and in vivo by targeting MCL1 gene

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