Polyphyllin I induces cell cycle arrest and apoptosis in human myeloma cells via modulating <i>β</i>‐catenin signaling pathway

Liang, Yun; Li, Xian; He, Xin; Qiu, Xi; Jin, Xueli; Zhao, Xiaoying; Xu, Rongzhen

doi:10.1111/ejh.12741

Cited by 25 publications

(17 citation statements)

References 24 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The foremost reported antitumor mechanism underlying the action of PPI was associated with the induction of apoptosis [5]. PPI induced cell apoptosis via activating the caspase cascade, inducing mitochondrial fragmentation [8], and modulating the β -catenin signaling pathway [9]. However, extensive investigation of the molecular pathways underlying PPI-induced apoptosis is required to determine the anticancer properties of this particular saponin.…”

Section: Introductionmentioning

confidence: 99%

Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells

Luo

Yang

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Polyphyllin has been reported to exhibit anticancer effects against various types of cancer via the proapoptotic signaling pathway. The aim of the present study was to investigate the role of the endoplasmic reticulum stress and death receptor signaling pathways in PPI-induced apoptosis of human hepatocellular carcinoma HepG2 cells. Analysis demonstrated that PPI could significantly inhibit the proliferation and induce apoptosis of HepG2 cells in a dose- and time-dependent manner. Investigation into the molecular mechanism of PPI indicated that PPI notably mediated ER stress activation via IRE-1 overexpression and activation of the caspase-12 to protect HepG2 cells against apoptosis. In addition, PPI markedly induced the expression of death receptors signaling pathways-associated factors, including tumor necrosis factor (TNF) receptor 1/TNF-α and FAS/FASL. Additionally, suppression of the death receptor signaling pathways with a caspase-8 inhibitor, Z-IETD-FMK, revealed an increase in the death rate and apoptotic rate of HepG2 cells. Collectively, the findings of the present study suggested that the ER stress and death receptor signaling pathways were associated with PPI-induced HepG2 cell apoptosis; however, endoplasmic reticulum stress may serve a protective role in this process. The combination of PPI and Z-IETD-FMK may activate necroptosis, which enhances apoptosis. Therefore, the results of the present study may improve understanding regarding the roles of signaling pathways in PPI regulated apoptosis and contribute to the development of novel therapies for the treatment of HCC.

show abstract

Section: Introductionmentioning

confidence: 99%

Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells

Luo

Yang

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…In the current study, our data showed a decrease in the proportion of CNE-2 cells at the G2/M phase of the cell cycle in the transfection group relative to the blank and negative control groups 24 h post-exposure to X-ray radiation, suggesting the relief of the cell cycle arrest at the G2/M phase, and the reduction in the proportion of CNE-2 cells at the G2/M phase resulted in relative radiation resistance in CNE-2 cells overexpressing β-catenin. Inhibition of β-catenin expression was found to significantly increase the proportion of hepatocellular carcinoma stem cells in the G2/M phase [45], and treatment with polyphyllin I (PPI), a major active constituent extracted from Paris polyphyllin, caused down-regulation of β-catenin expression in multiple myeloma cells and cell cycle arrest at G2/M phase [46]. These findings demonstrate the close correlation between β-catenin and cell cycle.…”

Section: Discussionmentioning

confidence: 81%

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

Kang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Nasopharyngeal carcinoma (NPC) is rare worldwide but remains highly prevalent in endemic regions, notably in southern China. Radiotherapy remains the treatment of choice for NPC, but radioresistance has been identified as a major cause of therapeutic failure. The Wnt/β-catenin signaling has been found to be involved in NPC radioresistance; however, the effect of β-catenin overexpression on radioresistance remains unknown in NPC until now. This study aimed to examine the impact of β-catenin overexpression on the radiosensitivity of human NPC CNE-2 cells. Methods: Immunohistochemistry was performed to detect the β-catenin expression in normal nasopharyngeal specimens and NPC specimens. The human NPC CNE-2 cell line overexpressing β-catenin was modeled by transfection with the pcDNA3.1/Hygro(+)/β-catenin recombinant vector (transfection group), while cells transfected with the pcDNA3.1/Hygro(+) vector served as negative controls and non-transfected cells served as blank controls. The expression of key molecules of the Wnt/β-catenin signaling pathway was determined using Western blotting and qPCR assays, and the changes of radiation sensitivity were measured with a colony-formation assay. Cell viability was measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide) assay. In addition, the cell cycle and apoptosis was detected using flow cytometry and the TCF/LEF transcriptional activity was measured with a Dual Luciferase Reporter Assay System. Results: Immunohistochemical staining showed high β-catenin expression in radioresistant NPC specimens, and low expression in radiosensitive NPC specimens and normal nasopharyngeal specimens. Western blotting and qPCR assays detected higher β-catenin expression in the transfection group than in the negative and blank controls (P < 0.01). Down-regulation of GSK-3β expression (P < 0.05) and up-regulation of Cyclin D1 expression (P < 0.01) was detected in β-catenin overexpressing NPC cells exposed to X-ray radiation relative to negative and blank controls. Colony-formation assay revealed higher D₀, D_q and SF in the transfection group than in the negative and blank control groups post-radiation, and the SER in the transfection group was 0.75-fold and 0.68-fold greater than that in the blank and negative control groups, respectively. MTT assay revealed that the viability of CNE-2 cells was significantly higher in the transfection group (96% ± 8.72%) than in the negative control group (74.67 ± 7.05%) and the blank control group (75.33% ± 7.02%) 24 h post-exposure to 6 Gy X-ray radiation (P < 0.05). X-ray radiation led to a lower proportion of CNE-2 cells at the G2/M phase and a lower apoptotic rate in the transfection group than in the negative and blank control groups (P < 0.05). In addition, the TCF/LEF transcriptional activity was higher in the transfection group than in the negative and blank control groups (P < 0.01), and 6 Gy X-ray radiation elevated the TCF/LEF transcriptional activity relative to 0 Gy radiation ...

show abstract

“…In a bortezomib-resistant lymphoma cell line, increased TCF4 expression and increased transcription by the TCF-4/β-catenin complex was observed, accompanied by upregulation of their downstream target genes (c-myc and cyclin D1) ( 8 ). In myeloma, the β-catenin inhibitors BC2059 ( 46 ) and polyphyllin I ( 49 ) have been shown to be efficacious in combination with bortezomib.…”

Section: Soluble Factor-mediated Drug Resistancementioning

confidence: 99%

Soluble and Cell–Cell-Mediated Drivers of Proteasome Inhibitor Resistance in Multiple Myeloma

Farrell

Reagan

2018

Front. Endocrinol.

View full text Add to dashboard Cite

It is becoming clear that myeloma cell-induced disruption of the highly organized bone marrow components (both cellular and extracellular) results in destruction of the marrow and support for multiple myeloma (MM) cell proliferation, survival, migration, and drug resistance. Since the first phase I clinical trial on bortezomib was published 15 years ago, proteasome inhibitors (PIs) have become increasingly common for treatment of MM and are currently an essential part of any anti-myeloma combination therapy. PIs, either the first generation (bortezomib), second generation (carfilzomib) or oral agent (ixazomib), all take advantage of the heavy reliance of myeloma cells on the 26S proteasome for their degradation of excessive or misfolded proteins. Inhibiting the proteasome can create a crisis specifically for myeloma cells due to their rapid production of immunoglobulins. PIs have relatively few side effects and can be very effective, especially in combination therapy. If PI resistance can be overcome, these drugs may prove even more useful to a greater range of patients. Both soluble and insoluble (contact mediated) signals drive PI-resistance via activation of various intracellular signaling pathways. This review discusses the currently known mechanisms of non-autonomous (microenvironment dependent) mechanisms of PI resistance in myeloma cells. We also introduce briefly cell-autonomous and stress-mediated mechanisms of PI resistance. Our goal is to help researchers design better ways to study and overcome PI resistance, to ultimately design better combination therapies.

show abstract

Polyphyllin I induces cell cycle arrest and apoptosis in human myeloma cells via modulating β‐catenin signaling pathway

Cited by 25 publications

References 24 publications

Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells

Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

Soluble and Cell–Cell-Mediated Drivers of Proteasome Inhibitor Resistance in Multiple Myeloma

Contact Info

Product

Resources

About