Guggulsterone inhibits human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell growth by inducing caspase-dependent apoptosis and downregulation of survivin and Bcl-2 expression

Zhong, Fei; Yang, Jing; Tong, Zhuting; Chen, Liuliu; Fan, Lulu; Wang, Fang; Zha, Xia-Li; Li, Jun

doi:10.3892/ol.2015.3391

Cited by 17 publications

(19 citation statements)

References 37 publications

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“…Treatment with 20mM DCA promotes robust cell death marked by extensive mitochondrial release of cytochrome c, indicative of apoptotic cell death ( S1 Fig ). Consistent with this immunofluorescent data, the addition of the pan-caspase inhibitor Z-VAD-FMK attenuated DCA cytotoxicity [ 38 , 39 ] ( S1 Fig ).…”

Section: Resultssupporting

confidence: 72%

Complex I inhibition augments dichloroacetate cytotoxicity through enhancing oxidative stress in VM-M3 glioblastoma cells

et al. 2017

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The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin’s reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination. Similarly, rotenone enhanced oxidative stress resultant from DCA treatment and this too was required for the noted augmentation of cytotoxicity. Adenosine monophosphate kinase (AMPK) activation was not observed with the concentration of metformin required to enhance DCA activity. Moreover, addition of an activator of AMPK did not enhance DCA cytotoxicity, whereas an inhibitor of AMPK heightened the cytotoxicity of the combination. Our data indicate that metformin enhancement of DCA cytotoxicity is dependent on complex I inhibition. Particularly, that complex I inhibition cooperates with DCA-induction of glucose oxidation to enhance cytotoxic oxidative stress in VM-M3 GBM cells.

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Section: Resultssupporting

confidence: 72%

Complex I inhibition augments dichloroacetate cytotoxicity through enhancing oxidative stress in VM-M3 glioblastoma cells

et al. 2017

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“…Previous studies have suggested survivin is upregulated in CCA tissues, and inhibition of survivin promoted cell apoptosis [10,11].…”

Section: Introductionmentioning

confidence: 91%

LncRNA FENDRR represses proliferation, migration and invasion through suppression of survivin in cholangiocarcinoma cells

Qin

Zhou

et al. 2019

Cell Cycle

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This study was to investigate the biological function and underlying mechanisms of FENDRR in cholangiocarcinoma (CCA) cell proliferation, migration and invasion. FENDRR and survivin expression in CCA tissues or cell lines were measured by qRT-PCR. In QBC939 and HuCCTl cells, cell proliferation was detected by CCK-8, cell migration and invasion were using transwell assay. RNA pull-down and RIP assay were performed to determine whether FENDRR can combine with SETDB1 in CCA cell. The effect of SETDB1 on survivin and H3K9me1 expression in CCA cells were determined by western blotting. ChIP analysis was performed to analyze the combination of SETDB1 with survivin promoter in CCA cell. The effect of SETDB1 knockdown on survivin and H3K9me1 expression in CCA cells after transfection with FENDRR were determined by western blotting. The results showed that lncRNA FENDRR was downregulated in CCA tissues and cells, and was negatively correlated with survivin expression. Further investigation demonstrated that FENDRR represses CCA cell proliferation, migration and invasion through regulating survivin expression. FENDRR associated with SETDB1 and H3K9 to epigenetically silence survivin and then regulated cell proliferation, migration and invasion. These findings indicate an important role for FENDRR-survivin axis in CCA cell proliferation, migration and invasion, and reveal a novel epigenetic mechanism for survivin silencing. Our data indicated that FENDRR silences survivin via SETDB1-mediated H3K9 methylation, thereby represses CCA cell proliferation, migration and invasion. ARTICLE HISTORY

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“…Alternatively, IGFBP-2 played an important role in cell proliferation, invasion, angiogenesis and apoptosis [32]. Simultaneously, Survivin as an important member of IAP, which were considered to be a regulator of apoptosis related proteins and prevention of apoptosis, and it was strongly expressed in CCA [33][34][35]. TNF-β also was identi ed as a key mediator between apoptosis and cancer cell progression [36].…”

Section: Discussionmentioning

confidence: 99%

GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration

Zhou¹,

Huang

Nie

et al. 2020

Preprint

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Background: Cholangiocarcinoma (CCA) is the second most common type of hepatocellular carcinoma with high aggressiveness and extremely poor prognosis. Homo sapiens germ cell associated 2 (GSG2) is a histone H3 threonine-3 kinase required for normal mitosis. Nevertheless, the role and mechanism of GSG2 in progression and development of CCA remain elusive. Methods: In the present study, correlation between GSG2 and CCA was elaborated by IHC, Mann-Whitney U and Spearman grading correlation. GSG2 knockdown cell lines were successfully constructed and further used to construct mouse xenotransplantation models. Subsequently, cell proliferation, cell apoptosis, cell cycle and cell migration were detected by MTT assay, Flow Cytometry and wound-healing assay, respectively. Results: It was demonstrated that GSG2 was overexpressed in CCA specimens and relevant cell lines. The statistical analysis determined that high GSG2 expression was positively associated with more advanced tumor grade. Importantly, GSG2 knockdown inhibited cell proliferation, migration, promoted cell apoptosis and arrested cell cycle in G2 phase. Meanwhile, in vivo results also supported that GSG2 knockdown inhibit tumor growth. Additionally, GSG2 was involved in CCA progression via suppressing EMT. Conclusions: In summary, our findings suggested that GSG2 may be a potential therapeutic target for CCA patients.

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Guggulsterone inhibits human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell growth by inducing caspase-dependent apoptosis and downregulation of survivin and Bcl-2 expression

Cited by 17 publications

References 37 publications

Complex I inhibition augments dichloroacetate cytotoxicity through enhancing oxidative stress in VM-M3 glioblastoma cells

Complex I inhibition augments dichloroacetate cytotoxicity through enhancing oxidative stress in VM-M3 glioblastoma cells

LncRNA FENDRR represses proliferation, migration and invasion through suppression of survivin in cholangiocarcinoma cells

GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration

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