Thiostrepton induces spindle abnormalities and enhances Taxol cytotoxicity in MDA-MB-231 cells.

ABSTRACT:

Background

Thiostrepton (TST) is a known inhibitor of the transcription factor Forkhead box M1 (FoxM1) and inducer of heat shock response (HSR) and autophagy. TST thus may be one potential candidate of anticancer drugs for combination chemotherapy.

Methods and results

Immunofluorescence staining of mitotic spindles and flow cytometry analysis revealed that TST induces mitotic spindle abnormalities, mitotic arrest, and apoptotic cell death in the MDA-MB-231 triple-negative breast cancer cell line. Interestingly, overexpression or depletion of FoxM1 in MDA-MB-231 cells did not affect TST induction of spindle abnormalities; however, TST-induced spindle defects were enhanced by inhibition of HSP70 or autophagy. Moreover, TST exhibited low affinity for tubulin and only slightly i

SUBMITTER: Kuo HH 

PROVIDER: S-EPMC11339111 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature