Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

Liu, Zhaojian; Qiao, Li; Xu, Bing; Wu, Jingjing; Guo, Chun; Zhu, Faliang; Yang, Qirong; Gao, Guimin; Gong, Yaoqin; Shao, Changshun

doi:10.1016/j.mrfmmm.2008.12.009

Cited by 126 publications

(95 citation statements)

References 38 publications

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“…Berberine could inhibit proliferations of all cell lines in dose-and time-dependent fashions. The anti-proliferative activity of berberine, however, is preferentially active on CCA cells rather than normal cholangiocytes, as the IC 50 of berberine to MMNK-1 was >30 times that of CCA cells at 72 h. This observation is similar to those reported for normal osteoblast cells, 16) Chang liver cells, a non-tumor liver cell line 17) and normal human keratinocytes.…”

Section: Discussionsupporting

confidence: 86%

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Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

Puthdee

Seubwai

Vaeteewoottacharn

et al. 2017

Biological & Pharmaceutical Bulletin

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Berberine is a natural compound found in several herbs. Anticancer activity of berberine was reported in several cancers, however, little is known regarding the effects of berberine against cholangiocarcinoma (CCA). In this study, the growth inhibitory effects of berberine on CCA cell lines and its molecular mechanisms were explored. Cell growth and cell cycle distribution were examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. The expression levels of cell cycle regulatory proteins were determined by Western blot analysis. Berberine significantly inhibited growth of CCA cell lines in a dose and time dependent fashion. The inhibition was largely attributed to cell cycle arrest at the G1 phase through the reduction of cyclin D1, and cyclin E. Moreover, berberine could reduce the expression and activation of signal transducers and activator of transcription 3 (STAT3) and probably nuclear factor-kappaB (NF-κB) via suppression of extracellular signal-regulated kinase (ERK) 1/2 action. These results highlight the potential of berberine to be a multi-target agent for CCA treatment.

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Section: Discussionsupporting

confidence: 86%

“…15) Similar results were also observed in an Ov-associated CCA hamster cell line. 16) The underlying molecular mechanisms of berberine induced cell cycle arrest and apoptosis in CCA cells, however, have remained unrevealed.…”

Section: Discussionmentioning

confidence: 99%

Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

Puthdee

Seubwai

Vaeteewoottacharn

et al. 2017

Biological & Pharmaceutical Bulletin

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“…SHG-44 cells appeared to be resistant to both berberine and temozolomide. Because its fluorescent nature, the intracellular accumulation of berberine can be visualized under fluorescence microscopy or detected by flow cytometry, and the cytotoxic effect of berberine depends on its intracellular accumulation (16). We observed that while the berberine-sensitive U87, U251, and U118 cells all exhibited remarkable intracellular accumulation of berberine, SHG-44 cells were devoid of berberine staining (data not shown), which may explain why the SHG-44 cells were more resistant to berberine than the other three cell lines.…”

Section: Resultsmentioning

confidence: 99%

Berberine Induces Senescence of Human Glioblastoma Cells by Downregulating the EGFR–MEK–ERK Signaling Pathway

Zhao

et al. 2015

Molecular Cancer Therapeutics

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108

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Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and has a poor prognosis. We, here, report a potent antitumor effect of berberine, an isoquinoline alkaloid, on GBM. Berberine was found to have an IC 50 that is much lower than temozolomide in vitro in U87, U251, and U118 glioblastoma cells. Although previous studies showed that berberine primarily exerts its anticancer effect by inducing cell-cycle arrest, apoptosis, and autophagy, we observed that the antitumor effect of berberine on glioblastoma cells was primarily achieved through induction of cellular senescence. In glioblastoma cells treated with berberine, the level of epidermal growth factor receptor (EGFR) was greatly reduced. Examination of the activities of the kinases downstream of EGFR revealed that the RAF-MEK-ERK signaling pathway was remarkably inhibited, whereas AKT phosphorylation was not altered. Pharmacologic inhibition or RNA interference of EGFR similarly induced cellular senescence of glioblastoma cells. Furthermore, the cellular senescence induced by berberine could be rescued by introduction of a constitutive active MKK. Berberine also potently inhibited the growth of tumor xenografts, which was accompanied by downregulation of EGFR and induction of senescence. Our findings thus revealed a new route by which berberine exerts its anticancer activity. Because EGFR is commonly upregulated in glioblastoma, the demonstration of effective inhibition of EGFR by berberine points to the possibility of using berberine in the treatment of patients with glioblastoma.

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“…Single-nucleotide polymolphisms of insulin-like growth factor 2 receptor are associated with an increased risk of OS (7). The phosphoprotein p53 gene as an anti-oncogene is associated with controlling the cell cycle in OS (8) and mutations in the p53 gene correlate significantly with the presence of high levels of genomic instability, which lead to cancerization in OS (9). Furthermore, microRNAs (miRs) play a significant role in cancer cell growth and migration; for example, miR-199a-3p decreases cell growth and migration in OS cell lines significantly (10).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

Yang

Wang

2016

Oncology Letters

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Abstract. The aim of this study was to explore the underlying molecular mechanism related to the process and progression of osteosarcoma (OS). The differentially expressed genes (DEGs) were downloaded from the Gene Expression Omnibus database. The pathway and gene ontology (GO) enrichment analysis, as well as transcription factor, tumor-associated gene and tumor suppressor gene analyses were performed to investigate the functions of DEGs. Next, the protein-protein interaction (PPI) network was constructed and module analysis was further assessed by cluster analysis with the overlapping neighborhood expansion (Cluster ONE) cytoscape plug-in. A total of 359 upregulated and 614 downregulated DEGs were identified to be differentially expressed between OS samples and normal controls. Pathways significantly enriched by DEGs included the focal adhesion and chromosome maintenance pathways. Significant GO terms were cell adhesion, cell cycle and nucleic acid metabolic processes. The upregulated PPI network was constructed with 170 nodes and the downregulated PPI network was constructed with 332 nodes. Breast-ovarian cancer gene 1 (BRCA1), melanocyte-stimulating hormone 2 (MSH2), cyclin D1 (CCND1) and integrin α5 (ITGA5) were identified to be hub proteins in PPI. In conclusion, the dysregulated genes played key roles in the progression of OS. Cell adhesion is a significant biological process in OS development, and the genes BRCA1, MSH2, CCND1 and ITGA5 may be potential targets in the therapy of OS.

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Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

Cited by 126 publications

References 38 publications

Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

Berberine Induces Senescence of Human Glioblastoma Cells by Downregulating the EGFR–MEK–ERK Signaling Pathway

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

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