Dual Inhibitors of P-gp and Carbonic Anhydrase XII (hCA XII) against Tumor Multidrug Resistance with Piperazine Scaffold DOI Creative Commons
Laura Braconi, Chiara Riganti, Astrid Parenti

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(14), P. 3290 - 3290

Published: July 11, 2024

A new series of piperazine derivatives were synthesized and studied with the aim obtaining dual inhibitors P-glycoprotein (P-gp) carbonic anhydrase XII (hCA XII) to synergistically overcome P-gp-mediated multidrug resistance (MDR) in cancer cells expressing two proteins, P-gp hCA XII. Indeed, these hybrid compounds contain both binding groups on nitrogen atoms heterocyclic ring. All showed good inhibitory activity each protein (P-gp individually, many them a synergistic effect resistant HT29/DOX A549/DOX cell lines which overexpress target proteins. In particular, compound 33 displayed best by enhancing cytotoxicity intracellular accumulation doxorubicin cells, thus resulting as promising MDR reverser mechanism. Furthermore, 13, 27 32 induced collateral sensitivity (CS) they more cytotoxic than sensitive ones; their CS mechanisms extensively investigated.

Language: Английский

Gaudichaudione H Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Disulfidptosis via Regulating NRF2‐SLC7A11 Signaling Pathway DOI Creative Commons

Mengjiao Shi,

Xinyan Li,

Ying Guo

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Gaudichaudione H (GH) is a naturally occurring small molecular compound derived from Garcinia oligantha Merr . (Clusiaceae), but the full pharmacological functions remain unclear. Herein, potential of GH in disulfidptosis regulation, novel form programmed cell death induced by disulfide stress explored. The omics results indicated that NRF2 signaling could be significantly activated GH. targets are associated with hepatocarcinogenesis and death. Moreover, both glutathione (GSH) metabolism NADP + ‐NADPH affected GH, indicating regulation. It also observed enhanced sensitivity hepatocellular carcinoma (HCC) cells to disulfidptosis, which dependent on activation NRF2‐SLC7A11 pathway. increased levels promoted transcription target gene, SLC7A11, through autophagy‐mediated non‐canonical mechanism. Under condition glucose starvation, GH‐induced upregulation SLC7A11 aggravated uptake cysteine, disturbance GSH synthesis, depletion NADPH, accumulation molecules, ultimately leading formation bonds between different cytoskeleton proteins eventually. Collectively, findings underscore role promoting cancer thereby offering promising avenue for treatment drug‐resistant HCC clinical settings.

Language: Английский

Citations

3
Broadening horizons: research on ferroptosis in lung cancer and its potential therapeutic targets DOI Creative Commons
Guangpeng Gao, Xindi Zhang

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 23, 2025

Ferroptosis is a novel form of cell death distinct from traditional mechanisms, characterized by the accumulation iron ions and production lipid peroxides. It not only affects survival tumor cells but also closely linked to changes in microenvironment. Lung cancer one leading malignancies worldwide terms incidence mortality, its complex biological mechanisms resistance make treatment challenging. Recent studies have shown that ferroptosis plays key role onset progression lung cancer, with intricate regulatory influencing development response therapy. As research into deepens, related molecular pathways, such as glutamate metabolism, antioxidant defense, been gradually revealed. However, clinical practice, ferroptosis-based therapeutic strategies for are still their early stages. Challenges remain, including incomplete understanding specific ferroptosis, insufficient on factors, limited insight interactions within Therefore, effective modulation enhance remains an urgent issue. This review summarizes analyzes factors interaction microenvironment, further explores potential targeting ferroptosis. By synthesizing latest research, this paper aims provide new perspectives directions treatment, goal advancing applications.

Language: Английский

Citations

0
Targeting PIM1 by Bruceine D attenuates skin fibrosis via myofibroblast ferroptosis DOI Creative Commons
Jianzhang Wang,

Yajuan Song,

Xiao-Ying Tan

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103619 - 103619

Published: March 1, 2025

Language: Английский

Citations

0
Natural prodigiosin from Serratia marcescens: a promising functional food colorant with iron chelation and antioxidative properties DOI

Shumei Ma,

Longhe Yang,

Huafeng Chen

et al.

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106490 - 106490

Published: March 1, 2025

Language: Английский

Citations

0
Infectious Spleen and Kidney Necrosis Virus Triggers Ferroptosis in CPB Cells to Enhance Virus Replication DOI Creative Commons
Qiushuang Zhang,

Ouqin Chang,

Qiang Lin

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(5), P. 713 - 713

Published: May 16, 2025

The role of ferroptosis—a novel iron-dependent programmed cell death pathway—in infectious spleen and kidney necrosis virus (ISKNV) infection remains poorly understood. Here, we demonstrate that ISKNV induces ferroptosis in CPB cells. Following challenge, cells exhibited hallmark morphological alterations including mitochondrial shrinkage, increased membrane density, cristae reduction. Biochemical assays confirmed significant time-dependent elevations markers: malondialdehyde (MDA, 1.7-fold), reactive oxygen species (ROS, 3.14-fold), ferrous iron (Fe2+, 1.42-fold) compared to controls (p < 0.05). Mechanistic studies revealed downregulated glutathione peroxidase 4 (GPx4) while upregulating acyl-CoA synthetase long-chain family member (ACSL4), as validated by quantitative real-time PCR (qRT-PCR) immunoblotting. Ferroptosis induction with erastin enhanced replication, whereas inhibition liproxstatin-1 suppressed viral yield. These findings establish exploits facilitate its pharmacological blockade this pathway significantly suppresses propagation, providing a new strategy intervention approach for controlling infection.

Language: Английский

Citations

0
Molecular Mechanisms of Potentilla Discolor Bunge in Regulating Ferroptosis to Alleviate DKD via the Nrf2 Signaling Pathway DOI
Yunhua Liu,

Yanmo Cai,

Xiaoyu Wei

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 120035 - 120035

Published: May 1, 2025

Language: Английский

Citations

0
Dual Inhibitors of P-gp and Carbonic Anhydrase XII (hCA XII) against Tumor Multidrug Resistance with Piperazine Scaffold DOI Creative Commons
Laura Braconi, Chiara Riganti, Astrid Parenti

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(14), P. 3290 - 3290

Published: July 11, 2024

A new series of piperazine derivatives were synthesized and studied with the aim obtaining dual inhibitors P-glycoprotein (P-gp) carbonic anhydrase XII (hCA XII) to synergistically overcome P-gp-mediated multidrug resistance (MDR) in cancer cells expressing two proteins, P-gp hCA XII. Indeed, these hybrid compounds contain both binding groups on nitrogen atoms heterocyclic ring. All showed good inhibitory activity each protein (P-gp individually, many them a synergistic effect resistant HT29/DOX A549/DOX cell lines which overexpress target proteins. In particular, compound 33 displayed best by enhancing cytotoxicity intracellular accumulation doxorubicin cells, thus resulting as promising MDR reverser mechanism. Furthermore, 13, 27 32 induced collateral sensitivity (CS) they more cytotoxic than sensitive ones; their CS mechanisms extensively investigated.

Language: Английский

Citations

1