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Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway.

Authors :
Qi Y
Wu H
Zhu T
Liu Z
Liu C
Yan C
Wu Z
Xu Y
Bai Y
Yang L
Cheng D
Zhang X
Zhao H
Zhao C
Dai X
Source :
Aging [Aging (Albany NY)] 2023 Aug 28; Vol. 15 (16), pp. 8258-8274. Date of Electronic Publication: 2023 Aug 28.
Publication Year :
2023

Abstract

Background: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity.<br />Methods: A heterograft mouse model using triple negative breast cancer (TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis.<br />Results: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro . In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal model of breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth.<br />Conclusions: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy.

Details

Language :
English
ISSN :
1945-4589
Volume :
15
Issue :
16
Database :
MEDLINE
Journal :
Aging
Publication Type :
Academic Journal
Accession number :
37651362
Full Text :
https://doi.org/10.18632/aging.204967