Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献

{"title":"Linarin alleviates high-fat diet-induced NAFLD via modulating the PI3K/Akt/mTOR pathway, autophagy, and gut microbiota.","authors":"Mengfan Lv, Yaxin Zhai, Hao Yu, Jiaqi Cheng, Yunfei Wei, Yibo Zhang, Yanmin Zhang, Haihua Feng","doi":"10.1016/j.bbalip.2025.159666","DOIUrl":"https://doi.org/10.1016/j.bbalip.2025.159666","url":null,"abstract":"<p><p>Linarin (Lin) is a flavonoid compound widely found in traditional herbal medicines and is recognized for its diverse biological properties, including anti-inflammatory, analgesic, antioxidant, hepatoprotective, and anti-apoptotic effects. Non-alcoholic fatty liver disease (NAFLD) is closely associated with autophagy and inflammation processes. However, the interaction between Lin and NAFLD remains underexplored. This study aimed to investigate the protective effects of Lin against NAFLD and its underlying pharmacological mechanisms. In vitro, we established a NAFLD model using AML12 cells stimulated with oleic acid (OA) and palmitic acid (PA). In vivo, we induced a chronic model in mice by feeding them a high-fat diet (HFD). Lipid metabolism markers, Oil Red O staining, and H&E staining were used to assess intracellular lipid accumulation. Inflammatory and autophagic markers were also measured. The 16S rRNA analysis was performed to evaluate the changes in the gut microbiota composition after Lin intervention in mice. Both in vitro and in vivo experiments demonstrated that Lin reduces lipid accumulation, which is mediated through the enhancement of autophagy and the inhibition of the release of inflammatory factors. 16S rRNA analysis revealed that Lin alleviates gut dysbiosis by reducing Firmicutes and Bacteroidetes phyla while increasing the abundance of Akkermansia and Bifidobacterium genera. Mechanistically, Lin activates autophagy via the PI3K/Akt/mTOR pathway, thereby alleviating lipid accumulation and inflammation. These findings suggest that Lin can mitigate NAFLD by inhibiting the activation of the PI3K/Akt/mTOR pathway, highlighting its potential as a promising therapeutic approach for NAFLD.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159666"},"PeriodicalIF":3.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of α-ketoglutarate on maternal lipid homeostasis and mitochondrial status perturbed by gestational arsenic exposure","authors":"Tong Zhan ,&nbsp;Shuang-Rui Bao ,&nbsp;Ying Sun ,&nbsp;Hong-Yan Wu ,&nbsp;Wen-Kang Tao ,&nbsp;Xin-Ru Liang ,&nbsp;Zhi-Yan Wan ,&nbsp;Qian Yang ,&nbsp;Hua Wang ,&nbsp;Yi-Chao Huang ,&nbsp;Jian-Qing Wang ,&nbsp;De-Xiang Xu ,&nbsp;Cheng Zhang","doi":"10.1016/j.bbalip.2025.159665","DOIUrl":"10.1016/j.bbalip.2025.159665","url":null,"abstract":"<div><div>Arsenic is a common environmental toxicant with known hepatotoxic effects, yet its impact on maternal lipid metabolism during pregnancy remains poorly understood. In this study, we established a pregnant mouse model to investigate the effects of gestational arsenic exposure and the potential protective role of α-ketoglutarate (α-KG), a key tricarboxylic acid (TCA) cycle intermediate. In the first experiment, arsenic exposure led to significant disruptions in maternal serum and hepatic lipid profiles. Mechanistically, arsenic reduced hepatic α-KG concentrations, impaired mitochondrial ultrastructure, altered mitochondria-related gene expression, induced oxidative stress, and decreased multiple TCA cycle intermediates, collectively indicating compromised mitochondrial function. In the second experiment, α-KG supplementation during gestation effectively restored hepatic α-KG levels and reversed arsenic-induced lipid metabolic imbalances. Moreover, α-KG preserved mitochondrial morphology, normalized the expression of mitochondrial genes, alleviated oxidative stress, and partially rescued the levels of disrupted TCA intermediates. These results suggest that arsenic disrupts maternal lipid homeostasis primarily through mitochondrial dysfunction and oxidative stress, and that α-KG supplementation can alleviate these disturbances by supporting mitochondrial function. Although the exact molecular mechanisms require further clarification, our findings highlight the potential therapeutic role of α-KG in maintaining maternal lipid metabolic health during arsenic exposure during pregnancy.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159665"},"PeriodicalIF":3.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin promotes lipid droplet-mitochondria coupling and improves insulin secretion in pancreatic β-cells exposed to lipotoxicity","authors":"Aneta M. Dobosz ,&nbsp;Ewelina Krogulec ,&nbsp;Nataniel Stefanowski ,&nbsp;Maria Kendziorek ,&nbsp;Magdalena Lebiedzinska-Arciszewska ,&nbsp;Mariusz R. Wieckowski ,&nbsp;Justyna Janikiewicz ,&nbsp;Agnieszka Dobrzyn","doi":"10.1016/j.bbalip.2025.159664","DOIUrl":"10.1016/j.bbalip.2025.159664","url":null,"abstract":"<div><div>Lipotoxicity that is caused by excess lipid accumulation is a major factor that contributes to gradual impairments of β-cell function and the development of type 2 diabetes. Metformin has shown protective effects against lipid-induced damage in β-cells, but its specific mechanisms of action within pancreatic islets remain unclear. The present study comprehensively examined direct effects of metformin on lipid metabolism pathways in INS-1E β-cells that were exposed to lipotoxic stress. Our results showed that metformin reduced both the number and size of lipid droplets in palmitate-treated INS-1E cells. This was followed by an increase in fatty acid utilization and the enhanced association between mitochondria and lipid droplets. Under conditions of palmitate overexposure, metformin limited the activity of adipose triglyceride lipase and lipogenic regulators, such as stearoyl-CoA desaturase, and suppressed fatty acid uptake into cells. Additionally, metformin alleviated triglyceride and free fatty acid accumulation and partially reversed palmitate-induced impairments in insulin secretion in INS-1E cells that were subjected to lipotoxicity. Notably, this beneficial effect of metformin on insulin secretion in INS-1E cells exposed to lipotoxic stress was less pronounced when the balance between mitochondrial fusion and fission was disturbed. These findings provide additional mechanistic insights into pleiotropic effects of metformin and its role in regulating β-cell function.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159664"},"PeriodicalIF":3.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of cytochrome P450-derived epoxy-fatty acids neuroprotection","authors":"Cynthia Navarro-Mabarak,&nbsp;Julio Morán","doi":"10.1016/j.bbalip.2025.159663","DOIUrl":"10.1016/j.bbalip.2025.159663","url":null,"abstract":"<div><div>The epoxyeicosatrienoic acids (EETs) are metabolites that result from the oxidation of the arachidonic acid by cytochrome P450 (CYP) epoxygenases. EETs are known to exert anti-inflammatory, antioxidant, vasodilatory, pro-angiogenic and anti-apoptotic actions. In the nervous system, EETs have been found to be neuroprotective in different models of neuronal damage. However, the molecular mechanisms responsible for these effects are not yet fully understood. This article seeks to review what is known about the signaling pathways involved in the EETs mediated neuroprotection. The mechanisms responsible for these effects are complex and involve several biological pathways that often crosstalk, including an inhibition of NFκB pathway, the activation of PPARα/γ nuclear receptors, and the activation of the PI3K/Akt pathway, among others. We also review what is known about the production and the biological significance of the epoxyeicosatrienoic acid ethanolamides (EET-EAs) and the epoxyeicosatrienoic acid glycerols (EET-EGs), metabolites that result from the epoxidation of the anandamide (AEA) and 2-arachidonylglycerol (2-AG) by CYP epoxygenases, which show endocannabinoid features.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159663"},"PeriodicalIF":3.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty acid binding protein 1 (FABP1) depletion promotes an oxidative metabolic shift in Caco-2 colorectal cancer cells.","authors":"Delfina Lucía Borús, Giorgia Zadra, Daniel Minsky, María Lucía Costa, Betina Córsico, Judith Storch, Natalia Scaglia","doi":"10.1016/j.bbalip.2025.159661","DOIUrl":"https://doi.org/10.1016/j.bbalip.2025.159661","url":null,"abstract":"<p><p>Lipid metabolism reprogramming is a well-established hallmark of many cancer types, including colorectal cancer (CRC). Nevertheless, a clear understanding on how fatty acid (FA) metabolism is fine-tuned during CRC development and progression is still missing. Given that CRC is the second leading cause of cancer-related death, addressing these critical aspects may provide the rationale for new therapeutic approaches and early biomarker identification. Fatty acid binding protein 1 (FABP1) is a small protein that binds FA and other lipophilic compounds, acting as a lipid transporter in the intestine. Little is currently known about the function of FABP1 in CRC. Here we show that the knockdown of FABP1 in CRC cells impairs de novo FA and cholesterol synthesis, specifically, via altering the transcriptional regulation of lipid metabolism genes. FABP1 depletion suppresses the expression of FA and cholesterol synthesis-associated genes while promoting that of FA oxidation genes and mitochondrial oxidative pathways. The latter is associated with increased oxygen consumption rate and activation of the energy sensor 5' AMP-activated kinase (AMPK). Taken together, our results show that FABP1 orchestrates the balance between FA synthesis and oxidation, most likely to prevent the cytotoxic effects of circulating unbound free fatty acids. Thus, targeting FABP1 function may represent a potential therapeutic strategy in advanced CRC.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159661"},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LIMP-2 deficiency-associated glycolipid abnormalities in mice","authors":"Paulo Gaspar ,&nbsp;André R.A. Marques ,&nbsp;Maria J. Ferraz ,&nbsp;Markus Damme ,&nbsp;Gertjan Kramer ,&nbsp;Mina Mirzaian ,&nbsp;Marion Gijbels ,&nbsp;Roelof Ottenhoff ,&nbsp;Cindy van Roomen ,&nbsp;Herman S. Overkleeft ,&nbsp;Michael Schwake ,&nbsp;Saskia Heybrock ,&nbsp;Maria Carmo Macário ,&nbsp;Paul Saftig ,&nbsp;Johannes M. Aerts","doi":"10.1016/j.bbalip.2025.159657","DOIUrl":"10.1016/j.bbalip.2025.159657","url":null,"abstract":"<div><div>Glucocerebrosidase (GCase) catalyzes the lysosomal degradation of glucosylceramide (GlcCer). GCase deficiency results in Gaucher disease (GD), a lysosomal storage disorder with characteristic hepatosplenomegaly. Transport of GCase to lysosomes is mediated by the lysosomal integral membrane protein type 2 (LIMP-2). Deficiency of LIMP-2 leads to reduced cellular GCase levels and manifests as Action Myoclonic Renal Failure Syndrome (AMRF). We investigated the cause for the markedly different symptomatology of GD and AMRF. In tissues of <em>Limp2 −/−</em> mice no prominent abnormalities in lysosomal enzymes were noted except for variable deficiency of GCase, as measured with enzymatic activity assay and detection of active GCase molecules with an activity-based probe. Noteworthy, in LIMP-2-deficient mice, residual GCase is remarkably high in leukocytes. GCase deficiency in tissues does not correlate with increases in GlcCer, but rather with increases in glucosylsphingosine (GlcSph) and glucosylated cholesterol (GlcChol), both glucosylated metabolites derived from GlcCer. Isolated lysosomes from hepatocytes of <em>Limp2 −/−</em> mice revealed no prominent abnormalities in lysosomal matrix proteins except GCase. The <em>Limp2 −/−</em> tritosomes showed clear increases in GlcSph and GlcChol but not in GlcCer. In conclusion, our data imply a critical role of LIMP-2 in glycosphingolipid homeostasis. Despite low GCase levels striking GlcCer accumulation is avoided in tissues of LIMP-2 deficient mice.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159657"},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partial inhibition of adipose CIDEC improves insulin sensitivity and increases energy expenditure in high-fat diet-fed mice via activating ATGL-PPARα pathway","authors":"Qinghua Fu ,&nbsp;Peng Wang ,&nbsp;Weilin Li ,&nbsp;Zhenhua Cai ,&nbsp;Shiji Zhao ,&nbsp;Weidong Ling ,&nbsp;Mingxun Li ,&nbsp;Xiaochuan Tang ,&nbsp;Ziyi Song","doi":"10.1016/j.bbalip.2025.159659","DOIUrl":"10.1016/j.bbalip.2025.159659","url":null,"abstract":"<div><div>Obesity poses a significant risk for metabolic disorders, such as insulin resistance and metabolic-associated fatty liver disease (MAFLD), yet effective treatments remain limited. Cell Death-Inducing DNA Fragmentation Factor-α-Like Effector C (CIDEC), a lipid droplet membrane protein, facilitates lipid droplet fusion and is crucial for adipose tissue expansion, making it a key target for obesity and related metabolic diseases. However, previous research revealed that complete genetic deletion of <em>Cidec</em> in adipose tissues, while reducing fat accumulation, induced severe insulin resistance in high-fat diet (HFD)-fed mice, potentially due to ectopic fat storage in the liver. Given that complete knockout is an extreme approach, partial inhibition holds greater clinical relevance. Therefore, this study aimed to investigate the effects of partial inhibition of CIDEC in adipose tissues on fat accumulation and insulin sensitivity in mice. Using the Cre-LoxP system, we generated adipose <em>Cidec</em> haploinsufficient mice. Under a standard diet, these mice exhibited normal body weight, fat accumulation, and insulin sensitivity. Notably, under HFD conditions, mice with partial <em>Cidec</em> deficiency showed reduced fat accumulation in adipose tissues while hepatic fat accumulation remained unchanged, accompanied by improved insulin sensitivity and increased energy expenditure. Mechanistically, we found partial <em>Cidec</em> deficiency activated thermogenic program in adipocytes <em>in vivo</em> and <em>in vitro</em> through the ATGL-PPARα pathway. In conclusion, adipose CIDEC partial inhibition attenuates HFD-induced obesity and insulin resistance by enhancing ATGL-PPARα-mediated energy expenditure, establishing this approach as a promising therapeutic strategy for obesity and related metabolic diseases.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159659"},"PeriodicalIF":3.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agonist- and stress-driven compartmentalized phosphoinositide signaling in cells","authors":"Mo Chen ,&nbsp;Jay Xiaojun Tan ,&nbsp;Yue Sun ,&nbsp;Narendra Thapa ,&nbsp;Vincent L. Cryns ,&nbsp;Richard A. Anderson","doi":"10.1016/j.bbalip.2025.159662","DOIUrl":"10.1016/j.bbalip.2025.159662","url":null,"abstract":"<div><div>Phosphoinositides (PIPs) are essential lipid messengers that regulate cellular responses to external stimuli and stress through spatially organized signaling pathways. In recent years, compartment-specific mechanisms by which PIP signaling integrates diverse cellular processes have been extensively expanded. This review discusses the distinct roles of PIP signaling across cellular compartments, including the plasma membrane, endosomes, lysosomes, protein scaffolds, and the nucleus. PIPs coordinate key processes such as receptor trafficking, cytoskeletal remodeling, autophagy, and signal transduction. Dynamic lysosomal PIP switches regulate critical functions like nutrient sensing, mTORC1 activity, and membrane repair, emphasizing their adaptability in maintaining cellular homeostasis. Furthermore, emerging evidence highlights nuclear PIP signaling in transcriptional regulation, DNA repair, and oncogenic pathways. Dysregulation of PIP signaling pathways is implicated in diseases such as cancer, neurodegeneration, and lysosomal storage disorders, underscoring their therapeutic potential in various pathological conditions.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159662"},"PeriodicalIF":3.9,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inositol 5-phosphatases OCRL and INPP5B: Cellular functions and roles in disease","authors":"Aloka de Sa ,&nbsp;Gaoyu Li ,&nbsp;Connor Byrne ,&nbsp;Martin Lowe","doi":"10.1016/j.bbalip.2025.159660","DOIUrl":"10.1016/j.bbalip.2025.159660","url":null,"abstract":"<div><div>OCRL and INPP5B are evolutionary conserved inositol 5-phosphatases that preferentially hydrolyse PI(4,5)P₂, a key regulator of numerous cellular processes. Mutation of OCRL causes Lowe syndrome and Dent-2 disease that manifest in the eye, brain and kidney, whereas mutations in INPP5B have not been reported to cause disease. Here, we provide a current view of the biology of both proteins, describing their subcellular locations, interaction partners and cellular processes they mediate or that are sensitive to their loss of function. There are many similarities in these properties between OCRL and INPP5B, albeit with some important differences. We also discuss the mechanisms underlying Lowe syndrome and Dent-2 disease, and the possible influence of INPP5B in dictating final phenotypic outcome. The knowledge gained studying OCRL and INPP5B has improved understanding of how cells function and will inform the design of new treatments for Lowe syndrome and Dent-2 disease and possibly other conditions.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159660"},"PeriodicalIF":3.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of minor cannabinoids on key pharmacological targets of estrogen receptor-positive breast cancer","authors":"Cristina Ferreira Almeida,&nbsp;Georgina Correia-da-Silva,&nbsp;Ana Paula Ribeiro,&nbsp;Natércia Teixeira,&nbsp;Cristina Amaral","doi":"10.1016/j.bbalip.2025.159658","DOIUrl":"10.1016/j.bbalip.2025.159658","url":null,"abstract":"<div><div>Endocrine therapy for estrogen receptor-positive (ER⁺) breast cancer has significantly improved over the last decades. However, it presents some limitations that make the search for novel therapeutic options mandatory. Several studies have been conducted to understand the anti-tumor potential of cannabinoids in breast cancer. Yet, most of them are focused on the major phytocannabinoids Δ⁹-tetrahydrocannabinol (<strong>THC</strong>) and cannabidiol (<strong>CBD</strong>). However, <em>Cannabis</em> has other minor phytocannabinoids whose anti-cancer properties are still to be elucidated. Here, we investigated the mechanisms of action of four minor cannabinoids, cannabigerol (<strong>CBG</strong>), cannabidivarin (<strong>CBDV</strong>), cannabinol (<strong>CBN</strong>), and cannabichromene (<strong>CBC</strong>), in 2D and 3D ER⁺ breast cancer models. These cannabinoids dysregulate MCF-7aro cell cycle progression, induce apoptosis by different mechanisms, and inhibit the growth of MCF-7aro spheroids. <strong>CBG</strong> exerts its effects through a down-regulation of both ER and AR protein levels, while <strong>CBDV</strong> reduces aromatase protein levels. <strong>CBN</strong> and <strong>CBC</strong> simultaneously affect the three targets, ER, aromatase, and AR. In fact, <strong>CBN</strong> and <strong>CBC</strong> present an AR-dependent cell death, down-regulate aromatase levels, and act as ER negative regulators impairing cancer cell growth. <strong>CBN</strong> caused the most pronounced effects. Overall, this study highlights the anti-cancer properties and the therapeutic potential of these minor cannabinoids in ER⁺ breast cancer.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159658"},"PeriodicalIF":3.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}