Tabersonine enhances cisplatin sensitivity by modulating Aurora kinase A and suppressing epithelial-mesenchymal transition in triple-negative breast cancer.
Pharm Biol
; 62(1): 394-403, 2024 Dec.
Article
in En
| MEDLINE
| ID: mdl-38739003
ABSTRACT
CONTEXT Tabersonine has been investigated for its role in modulating inflammation-associated pathways in various diseases. However, its regulatory effects on triple-negative breast cancer (TNBC) have not yet been fully elucidated. OBJECTIVE:
This study uncovers the anticancer properties of tabersonine in TNBC cells, elucidating its role in enhancing chemosensitivity to cisplatin (CDDP). MATERIALS ANDMETHODS:
After tabersonine (10 µM) and/or CDDP (10 µM) treatment for 48 h in BT549 and MDA-MB-231 cells, cell proliferation was evaluated using the cell counting kit-8 and colony formation assays. Quantitative proteomics, online prediction tools and molecular docking analyses were used to identify potential downstream targets of tabersonine. Transwell and wound-healing assays and Western blot analysis were used to assess epithelial-mesenchymal transition (EMT) phenotypes.RESULTS:
Tabersonine demonstrated inhibitory effects on TNBC cells, with IC50 values at 48 h being 18.1 µM for BT549 and 27.0 µM for MDA-MB-231. The combined treatment of CDDP and tabersonine synergistically suppressed cell proliferation in BT549 and MDA-MB-231 cells. Enrichment analysis revealed that the proteins differentially regulated by tabersonine were involved in EMT-related signalling pathways. This combination treatment also effectively restricted EMT-related phenotypes. Through the integration of online target prediction and proteomic analysis, Aurora kinase A (AURKA) was identified as a potential downstream target of tabersonine. AURKA expression was reduced in TNBC cells post-treatment with tabersonine. DISCUSSION ANDCONCLUSIONS:
Tabersonine significantly enhances the chemosensitivity of CDDP in TNBC cells, underscoring its potential as a promising therapeutic agent for TNBC treatment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cisplatin
/
Indole Alkaloids
/
Epithelial-Mesenchymal Transition
/
Triple Negative Breast Neoplasms
/
Aurora Kinase A
Limits:
Female
/
Humans
Language:
En
Journal:
Pharm Biol
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom