ReferenceID 1228

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

Phytother Res

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

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Reference Id
1228
Evidence Id
17818
Core Evidence Id
17818
Source Reference Id
2446
Herb2 Reference Id
HBREF003243
Subject Paper Key
HBIN017061_36444395
Pubmed Id
36444395
Doi
10.1002/ptr.7692
Paper Title
Asiaticoside hampers epithelial-mesenchymal transition by promoting PPARG expression and suppressing P2RX7-mediated TGF-β/Smad signaling in triple-negative breast cancer
Paper Abstract
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.
Journal
Phytother Res
Publish Year
2022
Experiment Subject
human; tnbc cells
Experiment Type
Cell Experiment
Phenotype Related
Metastases; Triple-negative Breast Cancer; Ductal Adenocarcinomas
Paper Title Cn
Paper Title En
Asiaticoside hampers epithelial-mesenchymal transition by promoting PPARG expression and suppressing P2RX7-mediated TGF-β/Smad signaling in triple-negative breast cancer
Bilingual Status
semi_complete