BUB1 Inhibition Induces Ferroptosis in Triple-Negative Breast Cancer Cell Lines DOI Creative Commons

Sushmitha Sriramulu,

Shivani Thoidingjam,

Stephen L. Brown

et al.

DNA, Journal Year: 2025, Volume and Issue: 5(1), P. 16 - 16

Published: March 12, 2025

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited effective treatments available, including targeted therapies, often leading to poor prognosis. Mitotic checkpoint kinase BUB1 frequently overexpressed in TNBC and correlates survival outcomes suggesting its potential as therapeutic target. This study explores the cytotoxicity of cells inhibition, alone or combination radiation demonstrates that ferroptosis, an iron-dependent form programmed cell death, has role. Methods: lines (SUM159, MDA-MB-231, BT-549) were treated inhibitor BAY1816032 (BUB1i) ferroptosis activator RSL3 without 4 Gy irradiation. Cell viability assays conducted assess treatment effects, qPCR analyses measured expression key markers ACSL4, GPX4, PTGS2, SLC7A11, NCOA4, IREB2, NFS1, TFRC expression, TBARS assay lipid peroxidation levels. Ferroptosis specificity was confirmed through co-treatment Ferrostatin-1 (F-1). Results: In all studied, inhibition significantly induced marked by increased ACSL4 decreased GPX4 The BUB1i further amplified these ferroptotic markers, at least additive effect, which not present radiation. Co-treatment reversed BUB1i-mediated death may involve signaling lines. Conclusions: independently induce lines, enhanced when combined activator. Further research warranted delineate molecular mechanism BUB1-mediated TNBC.

Language: Английский

Mechanisms of radiation‐induced tissue damage and response DOI Creative Commons

Zhou Lin,

Jiaojiao Zhu, Yuhao Liu

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 20, 2024

Radiation-induced tissue injury (RITI) is the most common complication in clinical tumor radiotherapy. Due to heterogeneity response of different tissues radiation (IR), radiotherapy will cause types and degrees RITI, which greatly limits application Efforts are continuously ongoing elucidate molecular mechanism RITI develop corresponding prevention treatment drugs for RITI. Single-cell sequencing (Sc-seq) has emerged as a powerful tool uncovering mechanisms identifying potential targets by enhancing our understanding complex intercellular relationships, facilitating identification novel cell phenotypes, allowing assessment spatiotemporal developmental trajectories. Based on comprehensive review we analyzed regulatory networks combination with Sc-seq summarized targeted intervention pathways therapeutic Deciphering diverse underlying can shed light its pathogenesis unveil new avenues potentially facilitate repair or regeneration currently irreversible Furthermore, discuss how personalized strategies based offer promise mitigating

Language: Английский

Citations

5

Comparative Analysis of Phytochemical Constituents of Ginkgo Biloba Flowers and Leaves, and Evaluation of Their Biological Activities DOI
Yuying Wang, Ruihong Li, Xin Sun

et al.

Published: Jan. 1, 2025

Ginkgo biloba L, as a Mesozoic relict tree species specialized in China, has attracted much attention for its unique chemical composition and pharmacological properties, most of the research focused on leaves (GBL). Our preliminary found that flowers (GBF) were superior to GBL terms anti-radiation activity, but underlying cause this discrepancy activity remains elusive. Therefore, present study aimed systematically compare nutritional compositions GBF investigate intrinsic mechanism their activities.In study, constituents identified by UPLC-Q-orbitrap HRMS, contents amino acids, fatty inorganic elements, purines, ceramides both determined. Meanwhile, activities exerted through regulation ferroptosis compared, focusing effect inhibiting ferroptosis.The results showed was indeed anti-ferroptosis exhibited more significant inhibitory regulating ferroptosis. Through in-depth analyses both, reveals possible material basis stronger provides theoretical support application nutraceuticals pharmaceuticals, especially development functional drugs with higher health benefits.

Language: Английский

Citations

0

BUB1 Inhibition Induces Ferroptosis in Triple-Negative Breast Cancer Cell Lines DOI Creative Commons

Sushmitha Sriramulu,

Shivani Thoidingjam,

Stephen L. Brown

et al.

DNA, Journal Year: 2025, Volume and Issue: 5(1), P. 16 - 16

Published: March 12, 2025

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited effective treatments available, including targeted therapies, often leading to poor prognosis. Mitotic checkpoint kinase BUB1 frequently overexpressed in TNBC and correlates survival outcomes suggesting its potential as therapeutic target. This study explores the cytotoxicity of cells inhibition, alone or combination radiation demonstrates that ferroptosis, an iron-dependent form programmed cell death, has role. Methods: lines (SUM159, MDA-MB-231, BT-549) were treated inhibitor BAY1816032 (BUB1i) ferroptosis activator RSL3 without 4 Gy irradiation. Cell viability assays conducted assess treatment effects, qPCR analyses measured expression key markers ACSL4, GPX4, PTGS2, SLC7A11, NCOA4, IREB2, NFS1, TFRC expression, TBARS assay lipid peroxidation levels. Ferroptosis specificity was confirmed through co-treatment Ferrostatin-1 (F-1). Results: In all studied, inhibition significantly induced marked by increased ACSL4 decreased GPX4 The BUB1i further amplified these ferroptotic markers, at least additive effect, which not present radiation. Co-treatment reversed BUB1i-mediated death may involve signaling lines. Conclusions: independently induce lines, enhanced when combined activator. Further research warranted delineate molecular mechanism BUB1-mediated TNBC.

Language: Английский

Citations

0