2D08 mediates notable anticancer effects through multiple cellular pathways in uterine leiomyosarcoma cells.
Oncol Rep
; 52(1)2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38874019
ABSTRACT
2',3',4'trihydroxyflavone (2D08), a SUMO E2 inhibitor, has several biological functions, including anticancer activity, but its effects on uterine leiomyosarcoma (UtLMS) are unknown. The anticancer activity of 2D08 was explored in an in vitro model using SKLMS1 and SKUT1B cells (human UtLMS cells). Treatment with 2D08 inhibited cell viability in a dose and timedependent manner and significantly inhibited the colonyforming ability of UtLMS cells. In SKUT1B cells treated with 2D08, flow cytometric analysis revealed a slight increase in apoptotic rates, while cell cycle progression remained unaffected. Western blotting revealed elevated levels of RIP1, indicating induction of necrosis, but LC3B levels remained unchanged, suggesting no effect on autophagy. A lactate dehydrogenase (LDH) assay confirmed increased LDH release, further supporting the induction of apoptosis and necrosis by 2D08 in SKUT1B cells. 2D08induced production of reactive oxygen species and apoptosis progression were observed in SKLMS1 cells. Using Ki67 staining and bromodeoxyuridine assays, it was found that 2D08 suppressed proliferation in SKLMS1 cells, while treatment for 48 h led to cellcycle arrest. 2D08 upregulated p21 protein expression in SKLMS1 cells and promoted apoptosis through caspase3. Evaluation of αSMactin, calponin 1 and TAGLN expression indicated that 2D08 did not directly initiate smooth muscle phenotypic switching in SKLMS1 cells. Transcriptome analysis on 2D08treated SKLMS1 cells identified significant differences in gene expression and suggested that 2D08 modulates cellcycle and apoptosisrelated pathways. The analysis identified several differentially expressed genes and significant enrichment for biological processes related to DNA replication and molecular functions associated with the apoptotic process. It was concluded that 2D08 exerts antitumor effects in UtLMS cells by modulating multiple signaling pathways and that 2D08 may be a promising candidate for the treatment of human UtLMS. The present study expanded and developed knowledge regarding UtLMS management and indicated that 2D08 represents a notable finding in the exploration of fresh treatment options for such cancerous tumors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Uterine Neoplasms
/
Apoptosis
/
Cell Proliferation
/
Leiomyosarcoma
Limits:
Female
/
Humans
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2024
Document type:
Article
Country of publication: