VSP-17, a New PPARγ Agonist, Suppresses the Metastasis of Triple-Negative Breast Cancer via Upregulating the Expression of E-Cadherin

Wang, Yuhui; Zhu, Mengyi; Yuan, Bo; Zhang, Kefeng; Zhong, Mingli; Yi, Wei; Xu, Xiequn; Duan, Xiaoqun

doi:10.3390/molecules23010121

Cited by 12 publications

(14 citation statements)

References 32 publications

(31 reference statements)

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“…VSP-17 (C 23 H 18 F 3 N 3 O, MW: 409.1402, purity ≥98%) was designed and synthesized by our team (Guangxi Colleges and Universities Key Laboratory of Pharmacology), the details of which have been described in our previous study ( 28 ). siAMPK (cat.…”

Section: Methodsmentioning

confidence: 99%

“…E-cadherin is a key marker of EMT (30). A previous study reported that VSP-17 treatment could upregulate the mRNA expression levels of E-cadherin in TNBC cells (28). To further determine the relationship between the activation of AMPK and the inhibition of the EMT process by VSP-17, MDA-MB-231 and MDA-MB-453 cells were treated with VSP-17 (10 µM) in combination with compound C (1 µM) or siAMPK transfection, respectively.…”

Section: Vsp-17 Treatment Suppresses the Migration And Invasion Of Tnmentioning

confidence: 99%

“…The present study aimed to determine the mechanism of action of the VSP-17-induced upregulation of E-cadherin levels in inhibiting TNBC metastasis, with a focus on the EMT and PPARγ/AMPK signaling pathways. C 23 H 18 F 3 N 3 O, MW: 409.1402, purity ≥98%) was designed and synthesized by our team (Guangxi Colleges and Universities Key Laboratory of Pharmacology), the details of which have been described in our previous study (28) Cell migration assay. According to the manufacturer's protocol, the cell migration assay was carried out using Transwell plates.…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence indicates that PPARγ is inactivated in TNBC cells, and its activation may inhibit the metastasis of breast cancer cells ( 26 , 27 ). VSP-17 has been identified as a novel PPARγ agonist, and it has been shown to suppress the metastasis of TNBC by upregulating the expression levels of E-cadherin ( 28 ). However, the mechanism through which VSP-17 may inhibit TNBC metastasis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

Yang

et al. 2020

Oncol Rep

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VSP-17, a novel peroxisome proliferator-activated receptor γ (PPARγ) agonist, has been previously demonstrated to suppress the metastasis of triple-negative breast cancer (TNBC) by upregulating the expression levels of E-cadherin, which is a key marker of epithelial-mesenchymal transition (EMT). However, the mechanism of action of VSP-17, in particular whether it may be associated with the EMT process, remains unknown. The present study investigated the ability of VSP-17 to inhibit the invasiveness and migratory ability of TNBC cell lines (MDA-MB-231 and MDA-MB-453) performed in in vitro experiments. including cell migration assay, cell invasion assay, cell transfection, RT-qPCR, western blot (WB) analysis and immunofluorescence. The present study aimed to ascertain whether and how the PPARγ/AMP-activated protein kinase (AMPK) signaling pathway serves a role in the inhibitory effects of VSP-17 on cell migration and invasion. The results revealed that both treatment with compound C (an AMPK inhibitor) and transfection with small interfering RNA (si)AMPK notably diminished the inhibitory effect of VSP-17 treatment on the migration and invasion of MDA-MB-231 and MDA-MB-453 cells, indicating that VSP-17 may, at least partly, exert its effects via AMPK. Furthermore, both compound C and siAMPK markedly diminished the VSP-17-induced downregulation of vimentin expression levels and upregulation of E-cadherin expression levels, further indicating that the VSP-17-induced inhibition of the EMT process may be dependent on AMPK. The combination of GW9662 (a PPARγ antagonist) or siPPARγ diminished the inhibitory effect of VSP-17 treatment on the migration and invasion of the TNBC cells, indicating that PPARγ may serve an important role in the VSP-17-induced inhibition of the migration and invasion of TNBC cells. In addition, both GW9662 and siPPARγ significantly reversed the VSP-17-induced downregulation of vimentin expression levels and upregulation of E-cadherin expression levels, implying that the VSP-17-induced inhibition of the EMT process may be dependent on PPARγ. VSP-17 treatment also upregulated the expression levels of p-AMPK, which could be reversed by either GW9662 or siPPARγ, indicating that the VSP-17-induced activation of the AMPK signaling pathway was PPARγ-dependent. In conclusion, the findings of the present study indicated that VSP-17 treatment may inhibit the migration and invasion of TNBC cells by suppressing the EMT process via the PPARγ/AMPK signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Vsp-17 Treatment Suppresses the Migration And Invasion Of Tnmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

Yang

et al. 2020

Oncol Rep

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“…In addition, a PPAR- γ agonist—rosiglitazone—reduces migration of both CAFs and breast cancer cells [ 121 ]. In addition, a novel PPAR- γ agonist VSP-17 inhibits TNBC metastasis via induction of E-cadherin [ 122 ]. Thymoquinone (TQ) is another compound that blocks CXCR4 expression in TNBC cells.…”

Section: Cxcl12/cxcr4-targeted Therapies Against Breast Cancermentioning

confidence: 99%

The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis

Zielińska

Katanaev

2020

Cancers

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The CXCL12/CXCR4 signaling pathway has emerged in the recent years as a key player in breast cancer tumorigenesis. This pathway controls many aspects of breast cancer development including cancer cell proliferation, motility and metastasis to all target organs. Moreover, the CXCL12/CXCR4 cascade affects both immune and stromal cells, creating tumor-supporting microenvironment. In this review, we examine state-of-the-art knowledge about detrimental roles of the CXCL12/CXCR4 signaling, discuss its therapeutic potential and suggest further research directions beneficial both for basic research and personalized medicine in breast cancer.

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Asiaticoside hampers epithelial–mesenchymal transition by promoting PPARG expression and suppressing P2RX7‐mediated TGF‐β/Smad signaling in triple‐negative breast cancer

Huang

Jia

et al. 2022

Phytotherapy Research

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Triple-negative breast cancer (TNBC) accounts for 10-20% of all human ductal adenocarcinomas and has a poor prognosis relative to other subtypes because of its high propensity to develop metastases. Here, the anticancer effects of asiaticoside (AC) against TNBC and the possible underlying mechanism were examined. We found that AC inhibited the TGF-β1 expression and the SMAD2/3 phosphorylation in TNBC cells, thereby impairing the TGF-β/SMAD signaling. AC inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells by suppressing the TGF-β/SMAD signaling. Meanwhile, AC inhibited the lung metastasis of TNBC cells in vivo and the expression of p-SMAD2/3 and vimentin, and increased the expression of E-cadherin and ZO-1 in the lung. Peroxisome proliferator activated receptor gamma (PPARG) was identified as a potential target of AC. AC increased PPARG expression, while PPARG knockdown attenuated the therapeutic effect of AC. AC-mediated PPARG overexpression suppressed the transcription of P2X purinoceptor 7 (P2RX7). The restoration of P2RX7 reversed the therapeutic effect of AC. These results suggested that AC blocked P2RX7-mediated TGF-β/SMAD signaling by increasing PPARG expression, thereby suppressing EMT in TNBC.

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VSP-17, a New PPARγ Agonist, Suppresses the Metastasis of Triple-Negative Breast Cancer via Upregulating the Expression of E-Cadherin

Cited by 12 publications

References 32 publications

VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis

Asiaticoside hampers epithelial–mesenchymal transition by promoting PPARG expression and suppressing P2RX7‐mediated TGF‐β/Smad signaling in triple‐negative breast cancer

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