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

Cholesterol effects on the tumor immune microenvironment: from fundamental concepts to mechanisms and implications DOI Creative Commons
Francisco Alejandro Lagunas‐Rangel

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 9, 2025

In many cancers, the tumor microenvironment is enriched with cholesterol due to increased biosynthesis and uptake by cancer cells, resulting in accumulation of cholesterol, esters, oxysterols other metabolites various functions. These molecules serve as structural components, energy sources intracellular signaling mediators, while their toxic by-products are secreted suppress anti-tumor immune activity prevent lipid peroxidation that could induce cell apoptosis. Immune cells also contribute dynamics. Tumor-associated macrophages (TAMs) release support metabolism, myeloid-derived suppressor (MDSCs) consume essential such L-arginine, which impairs T-cell proliferation activation. Elevated dendritic migration antigen presentation and, lymphocytes, favors development a regulatory T (Treg) phenotype inhibits antitumor cytokines, further weakening response. findings suggest targeting metabolism promising strategy for treatment, improving efficacy checkpoint blockade (ICB) therapies. this manuscript, molecular mechanisms underlying effects on landscape reviewed potential cholesterol-lowering drugs enhance responses explored.

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.

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