Lipid droplet formation induced by icaritin derivative IC2 promotes a combination strategy for cancer therapy DOI Creative Commons

Guosheng Wu,

Ying Liang, Qian Zhang

et al.

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: Dec. 26, 2024

Abstract Background Lipid metabolism is crucial in cancer progression. droplets (LDs) generated cells can act as protective mechanisms through alleviating lipotoxicity under stress conditions. We previously developed IC2 from the Chinese medicine icaritin an inhibitor of stearoyl-CoA desaturase 1 (SCD1). has been shown to disrupt lipid and inhibits cell proliferation. However, impact on intracellular LDs potential targeting LD formation for combination therapy remain unexplored. Methods was analyzed with oil red O or BODIPY staining by microscopy. quantification normalized number. IC2-induced cellular responses were revealed transcriptional analysis, real-time PCR, immunoblotting. Mitochondrial functions assessed measuring ATP production oxygen consumption. The source studied using transporter inhibitors deprivation. effect inhibiting IC2's anti-tumor effects evaluated MTT assays apoptosis assays, which subsequently validated vivo xenografted tumor model. Results exerted effects, resulting various cells. stimulated independent extracellular sources did not result increased de novo fatty acid (FA) synthesis within Transcriptional analysis indicated that disturbed mitochondrial functions, confirmed impaired membrane (MMP) reduced capacity Moreover, treatment led a greater accumulation lipids outside mitochondria compared control group. inhibited proliferation PC3 promoted These further enhanced after diacylglycerol acyltransferase (DGAT1), key enzyme involved formation. In PC3-xenografted mice, DGAT1 augmented reduction growth modulating Conclusion feedback response IC2’s compromises actions. efficacy be combining it This strategy may extended other agents regulate metabolism.

Language: Английский

A Novel Prognostic Signature of Mitophagy-Related E3 Ubiquitin Ligases in Breast Cancer DOI Open Access

Kangjing Bian,

Chihyu Yang, Feng Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1551 - 1551

Published: Feb. 12, 2025

Mitophagy plays a critical role in maintaining mitochondrial quality and cellular homeostasis. But the specific contribution of mitophagy-related E3 ubiquitin ligases to prognoses remains largely unexplored. In this study, we identified novel ligase prognostic signature using least absolute shrinkage selector operator (LASSO) multivariate Cox regression analyses breast cancer. Based on median risk scores, patients were divided into high-risk low-risk groups. Functional enrichment conducted explore biological differences between two Immune infiltration, drug sensitivity, mitochondrial-related phenotypes also analyzed evaluate clinical implications model. A four-gene (ARIH1, SIAH2, UBR5, WWP2) was identified, Kaplan-Meier analysis demonstrated that group had significantly worse overall survival (OS). The exhibited disrupted metabolism immune dysregulation with upregulated checkpoint molecules. Additionally, higher sensitivity several drugs targeting Akt/PI3K/mTORC1 signaling axis. Accompanying metabolic dysregulation, mtDNA stress elevated, contributing activation senescence-associated secretory phenotype (SASP) group. conclusion, provides robust tool for stratification offers insights interplay mitophagy, modulation, therapeutic responses

Language: Английский

Citations

0
Discovery of a new mitophagy-related gene signature for predicting the outlook and immunotherapy in triple-negative breast cancer DOI Creative Commons
Gang Liu,

Guozheng Yu,

Dongzhi Yin

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 25, 2025

Mitophagy is an essential cellular process that conserved and crucial for maintaining balance by selectively eliminating malfunctioning mitochondria. However, there still limited knowledge regarding the influence of mitophagy-related genes (MRGs) on prognosis response to treatment triple-negative breast cancer (TNBC). In here, TCGA GEO databases were used acquire transcriptomic clinical information patients with TNBC, correspondingly. Using LASSO multivariable Cox regression analyses, a risk signature related mitophagy was established based prognostic MRGs. The associated consisted five (BSG, JMJD6, DNAJA3, DISC1, SQSTM1) independently predicted regardless factors (p < 0.05). Patients classified within high-risk group demonstrated significantly lower overall survival rates when contrasted those in low-risk group. model exhibited excellent performance predicting stratification, as evidenced receiver operating characteristic C-index. findings stayed unchanged following external validation. Moreover, we observed notable variation tumor immune microenvironment among different categories. low TNBC more favorable immunotherapy compared high risk. conclusion, our study uncovered possible impacts MRGs microenvironment, pathological characteristics, outlook TNBC. CRG-related strongly linked against has potential serve valuable tool patients.

Language: Английский

Citations

0
Repurposing chlorpromazine for the treatment of triple-negative breast cancer growth and metastasis based on modulation of mitochondria-mediated apoptosis and autophagy/mitophagy DOI

Yamin Pu,

Fuyan Xu,

Anqi He

et al.

British Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

Citations

0
PI3K and PINK1 Immunoexpression as Predictors of Survival in Patients Undergoing Resection of Brain Metastases from Lung Adenocarcinoma DOI Open Access
Miriam Rubiera-Valdés, María D. Corte‐Torres,

Andrea Navarro-López

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2945 - 2945

Published: March 24, 2025

Phosphoinositide 3-kinase (PI3K) and PTEN-induced kinase 1 (PINK1) are key regulators of metabolism mitochondrial quality control. This study assessed their immunoexpression in 22 patients with lung adenocarcinoma resected brain metastases who underwent curative treatment between 2007 2017 evaluated prognostic significance. Tissue microarrays primary tumors matched were analyzed using the H-score method. PI3K expression was significantly higher (96.8 ± 57.9 vs. 43.5 62.3; p = 0.003) stage IV adenocarcinomas (113.3 56.3 61.4 47.1; 0.043). PINK1 showed no significant variation across disease stages. Univariate analysis identified older age (>55 years), overexpression (HR 7.791, 95% CI 1.718-36.432; >50 points), (>100 points) as predictors poor overall survival 2.236, 1.109-4.508; 0.025). Multivariate confirmed an independent factor 4.328, 1.264-14.814; 0.020). These findings suggest that may serve biomarkers metastases, emphasizing need for research on role tumor progression therapeutic response.

Language: Английский

Citations

0
A review on fumonisin B1-induced mitochondrial dysfunction and its impact on mitophagy and DNA methylation DOI Creative Commons

Algasan Govender,

Anil A. Chuturgoon, Terisha Ghazi

et al.

Food and Chemical Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 115458 - 115458

Published: April 1, 2025

Language: Английский

Citations

0
Harmine-Induced Disruption of the Blood-Brain Barrier via Excessive Mitophagy in Zebrafish DOI
Yi Wu,

Menghui He,

Ying He

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 177223 - 177223

Published: Dec. 1, 2024

Language: Английский

Citations

1
Lipid droplet formation induced by icaritin derivative IC2 promotes a combination strategy for cancer therapy DOI Creative Commons

Guosheng Wu,

Ying Liang, Qian Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Abstract Background Lipid metabolism is crucial in cancer progression. droplets (LDs) generated cells can act as protective mechanisms through alleviating lipotoxicity under stress conditions. We previously developed IC2 from the Chinese medicine icaritin an inhibitor of stearoyl-CoA desaturase 1 (SCD1). has been shown to disrupt lipid and inhibits cell proliferation. However, impact on intracellular LDs potential targeting LD formation for combination therapy remain unexplored.Methods was analyzed with oil red O or BODIPY staining by microscopy. quantification normalized number. IC2-induced cellular responses were revealed transcriptional analysis, real-time PCR, immunoblotting. Mitochondrial functions assessed measuring ATP production oxygen consumption. The source studied using transporter inhibitors deprivation. effect inhibiting IC2's anti-tumor effects evaluated MTT assays apoptosis assays, which subsequently validated in vivo xenografted tumor model.Results exerted effects, resulting various cells. stimulated independent extracellular sources did not result increased de novo fatty acid (FA) synthesis within Transcriptional analysis indicated that disturbed mitochondrial functions, confirmed impaired membrane (MMP) reduced capacity Moreover, treatment led a greater accumulation lipids outside mitochondria compared control group. inhibited proliferation PC3 promoted These further enhanced after diacylglycerol acyltransferase (DGAT1), key enzyme involved formation. In PC3-xenografted mice, DGAT1 augmented reduction growth modulating formation.Conclusion feedback response compromises actions. IC2’s efficacy be combining it This strategy may extended other agents regulate metabolism.

Language: Английский

Citations

0
Lipid droplet formation induced by icaritin derivative IC2 promotes a combination strategy for cancer therapy DOI Creative Commons

Guosheng Wu,

Ying Liang, Qian Zhang

et al.

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: Dec. 26, 2024

Abstract Background Lipid metabolism is crucial in cancer progression. droplets (LDs) generated cells can act as protective mechanisms through alleviating lipotoxicity under stress conditions. We previously developed IC2 from the Chinese medicine icaritin an inhibitor of stearoyl-CoA desaturase 1 (SCD1). has been shown to disrupt lipid and inhibits cell proliferation. However, impact on intracellular LDs potential targeting LD formation for combination therapy remain unexplored. Methods was analyzed with oil red O or BODIPY staining by microscopy. quantification normalized number. IC2-induced cellular responses were revealed transcriptional analysis, real-time PCR, immunoblotting. Mitochondrial functions assessed measuring ATP production oxygen consumption. The source studied using transporter inhibitors deprivation. effect inhibiting IC2's anti-tumor effects evaluated MTT assays apoptosis assays, which subsequently validated vivo xenografted tumor model. Results exerted effects, resulting various cells. stimulated independent extracellular sources did not result increased de novo fatty acid (FA) synthesis within Transcriptional analysis indicated that disturbed mitochondrial functions, confirmed impaired membrane (MMP) reduced capacity Moreover, treatment led a greater accumulation lipids outside mitochondria compared control group. inhibited proliferation PC3 promoted These further enhanced after diacylglycerol acyltransferase (DGAT1), key enzyme involved formation. In PC3-xenografted mice, DGAT1 augmented reduction growth modulating Conclusion feedback response IC2’s compromises actions. efficacy be combining it This strategy may extended other agents regulate metabolism.

Language: Английский

Citations

0