Triptolide induces apoptosis of breast cancer cells via a mechanism associated with the Wnt/β-catenin signaling pathway

Shao, Hongmin; Ma, Jinghua; Guo, Tianhua; Hu, Rongrong

doi:10.3892/etm.2014.1729

Cited by 42 publications

(30 citation statements)

References 21 publications

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“…The results indicated that the Wnt pathway participated in the development of vascular mimicry and cell proliferation induced by shRNA-Pygo2. Previous studies have also transfected the siRNA sequences specific to Pygo protein mRNA, and inhibited the TCF/LEF-mediated transcriptional activation of reporter genes (30,31), which suggested that Pygo2 members may be involved in TCF/β-catenin-driven transcription. In the present study, the expression of cyclin D1 protein in the U251 cells treated with shRNA-Pygo2 was investigated.…”

Section: A B Cmentioning

confidence: 99%

Downregulation of Pygopus 2 inhibits vascular mimicry in glioma U251 cells by suppressing the canonical Wnt signaling pathway

Wang

et al. 2015

Oncology Letters

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Abstract. Gliomas are the most common type of malignant primary brain tumor, and the Wnt signaling pathway is associated with glioma malignancy. Pygopus protein plays an important role in developmental brain patterning, and has been identified to be a component of the Wnt signaling pathway. In the present study, the Pygopus 2 (Pygo2) protein was examined in 80 glioma tissue samples. Short hairpin (sh) RNA-Pygo2 was transfected into glioma U251 cells, and the cell proliferation, colony formation and bromodeoxyuridine (BrdU) incorporation were analyzed. Western blot analysis and reverse transcription-polymerase chain reaction were used to detect the expression of Pygo2. A vascular mimicry assay was performed to examine the vascular mimicry of U251 cells. A luciferase reporter assay was used to detect the β-catenin/Wnt system. The cyclin D1 protein was also detected using western blot analysis. The results demonstrated that inhibition of the expression of Pygo2 significantly triggered the decrease of cell proliferation, colony formation and BrdU incorporation compared with the cells treated with scramble control shRNA (shRNA-Scr). shRNA-Pygo2 transfection was found to inhibit vascular-mimicry and block the Wnt signaling pathway compared to the cells transfected with shRNA-Scr. The transfection of shRNA-Pygo2 also decreased the expression of the Wnt target gene cyclin D1. In conclusion, shRNA-Pygo2 suppressed glioma cell proliferation effectively and inhibited vascular mimicry by inhibiting the expression of cyclin D1 in the canonical Wnt/β-catenin pathway in brain glioma cells.

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Section: A B Cmentioning

confidence: 99%

Downregulation of Pygopus 2 inhibits vascular mimicry in glioma U251 cells by suppressing the canonical Wnt signaling pathway

Wang

et al. 2015

Oncology Letters

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“…Previously triptolide was reported to attenuate Wnt3a-CM-induced β-catenin protein levels in a dose dependent manner1317. We examined whether triptonide has a similar effect on β-catenin levels using the active non-phosphorylated β-catenin antibody.…”

Section: Resultsmentioning

confidence: 99%

Triptonide Effectively Inhibits Wnt/β-Catenin Signaling via C-terminal Transactivation Domain of β-catenin

Chinison

Aguilar

Avalos

et al. 2016

Sci Rep

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Abnormal activation of canonical Wnt/β-catenin signaling is implicated in many diseases including cancer. As a result, therapeutic agents that disrupt this signaling pathway have been highly sought after. Triptonide is a key bioactive small molecule identified in a traditional Chinese medicine named Tripterygium wilfordii Hook F., and it has a broad spectrum of biological functions. Here we show that triptonide can effectively inhibit canonical Wnt/β-catenin signaling by targeting the downstream C-terminal transcription domain of β-catenin or a nuclear component associated with β-catenin. In addition, triptonide treatment robustly rescued the zebrafish “eyeless” phenotype induced by GSK-3β antagonist 6-bromoindirubin-30-oxime (BIO) for Wnt signaling activation during embryonic gastrulation. Finally, triptonide effectively induced apoptosis of Wnt-dependent cancer cells, supporting the therapeutic potential of triptonide.

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“…The associated molecular mechanisms by which TPL inhibits breast cancer cells have been investigated. n In breast cancer, TPL induces p53-dependent and lysosomal-mediated apoptosis, and inhibits numerous oncogenic signaling pathways, including the Wnt/β-catenin, the protein kinase B (Akt) and the focal adhesion kinase-signaling pathway (3,10,11). Notably, TPL inhibits key transcriptional factors, including MYC and estrogen receptor (ER), which suppresses associated target networks (12,13).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of insulin‑like growth factor 1 signaling synergistically enhances the tumor suppressive role of triptolide in triple‑negative breast cancer cells

Sun

2019

Oncol Lett

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Triptolide (TPL) is an active extract from a Chinese herb, which has been used for centuries in China. TPL exhibits numerous bioactivities and pharmacological effects, including antitumor, anti-inflammatory and immunosuppressive activities. However, previous studies have further revealed a multi-target toxicity of TPL, including reproductive toxicity, hepatotoxicity and renal cytotoxicity. To validate the clinical benefit and reduce the risk of TPL application, studies have investigated the combination of TPL with other reagents to allow lower doses and decrease toxicity. The present study reported that TPL and the insulin-like growth factor-1 receptor (IGF1R) inhibitor AG1024synergistically inhibited cell proliferation and induced apoptosis in triple-negative breast cancer cells. Overexpression of B-cell lymphoma 2 partially reversed the TPL and AG1024-induced increase in apoptosis. A similar synergistic effect was observed with a combination of AG1024 and cisplatin, a DNA damage inducer, in MDA-MB-231 cells. These results suggested that inhibition of IGF1R may sensitize triple-negative breast cancer cells to DNA damage inducers. Using publicly available data from The Cancer Genome Atlas, an amplification and gain of copy number of IGF1R was observed in 38% of triple-negative breast tumors (n=82), 26% of estrogen receptor (ER)-negative tumors (n=174) and 10% of ER-positive tumors (n=594). Similarly, a higher alteration frequency of IGF1R was identified in basal-like breast tumors compared with luminal A/B-like breast tumors. Overexpressed proteins associated with these alterations were revealed to be significantly enriched in multiple oncogenic signaling pathways, key transcription factor networks and DNA repair pathways. In summary, the present study suggested that inhibition of IGFR signaling and induction of DNA damage may exhibit synergistic effects for the treatment of triple-negative and ER-negative breast cancer.

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Triptolide induces apoptosis of breast cancer cells via a mechanism associated with the Wnt/β-catenin signaling pathway

Cited by 42 publications

References 21 publications

Downregulation of Pygopus 2 inhibits vascular mimicry in glioma U251 cells by suppressing the canonical Wnt signaling pathway

Downregulation of Pygopus 2 inhibits vascular mimicry in glioma U251 cells by suppressing the canonical Wnt signaling pathway

Triptonide Effectively Inhibits Wnt/β-Catenin Signaling via C-terminal Transactivation Domain of β-catenin

Inhibition of insulin‑like growth factor 1 signaling synergistically enhances the tumor suppressive role of triptolide in triple‑negative breast cancer cells

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