Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status DOI Creative Commons
Fábio Alessandro de Freitas, Débora Levy, Amira Zarrouk

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(9), P. 2301 - 2301

Published: Sept. 3, 2021

Oxysterols are oxidized derivatives of cholesterol produced by enzymatic activity or non-enzymatic pathways (auto-oxidation). The oxidation processes lead to the synthesis about 60 different oxysterols. Several oxysterols have physiological, pathophysiological, and pharmacological activities. effects on cell death processes, especially apoptosis, autophagy, necrosis, oxiapoptophagy, as well their action proliferation, reviewed here. These effects, also observed in several cancer lines, could potentially be useful treatment. differentiation described. Among them, properties stimulating osteogenic mesenchymal stem cells while inhibiting adipogenic may regenerative medicine.

Language: Английский

Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response DOI Creative Commons
Radha Desai, Daniel A. East, Liana Hardy

et al.

Science Advances, Journal Year: 2020, Volume and Issue: 6(51)

Published: Dec. 18, 2020

Physical tethering between mitochondria and nucleus sustains retrograde response.

Language: Английский

Citations

109
Cholesterol Metabolic Reprogramming in Cancer and Its Pharmacological Modulation as Therapeutic Strategy DOI Creative Commons
Isabella Giacomini,

Federico Gianfanti,

María Andrea Desbats

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: May 24, 2021

Cholesterol is a ubiquitous sterol with many biological functions, which are crucial for proper cellular signaling and physiology. Indeed, cholesterol essential in maintaining membrane physical properties, while its metabolism involved bile acid production steroid hormone biosynthesis. Additionally, isoprenoids metabolites of the mevalonate pathway support protein-prenylation dolichol, ubiquinone heme Cancer cells rely on to satisfy their increased nutrient demands uncontrolled growth, thus promoting tumor development progression. transformed reprogram either by increasing uptake de novo biosynthesis, or deregulating efflux. Alternatively, can efficiently accumulate into lipid droplets deeply modify activity key homeostasis regulators. In light these considerations, altered pathways might represent intriguing pharmacological targets exploitable strategies context cancer therapy. Thus, this work aims discuss emerging evidence vitro vivo studies, as well clinical trials, role treatment cancer, starting from already available cholesterol-lowering drugs (statins fibrates), moving towards novel potential inhibitors selective target modulators.

Language: Английский

Citations

87
Lipids and Lipid-Processing Pathways in Drug Delivery and Therapeutics DOI Open Access
Milica Marković, Shimon Ben‐Shabat, Aaron Aponick

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(9), P. 3248 - 3248

Published: May 4, 2020

The aim of this work is to analyze relevant endogenous lipid processing pathways, in the context impact that lipids have on drug absorption, their therapeutic use, and utilization delivery. Lipids may serve as biomarkers some diseases, but they can also provide effects for certain pathological conditions. Current uses possible clinical benefits various (fatty acids, steroids, triglycerides, phospholipids) cancer, infectious, inflammatory, neurodegenerative diseases are presented. be conjugated a molecule, accomplishing numerous potential benefits, one being improved treatment effect, due joined influence carrier moiety. In addition, such conjugates increased lipophilicity relative parent drug. This leads pharmacokinetics bioavailability, ability join pathways achieve targeting lymphatics, inflamed tissues autoimmune or enable overcoming different barriers body. Altogether, novel mechanisms role constantly discovered, new ways exploit these optimal design would advance delivery/therapy aspects continuously emerging.

Language: Английский

Citations

74
Lipid Metabolism in Oncology: Why It Matters, How to Research, and How to Treat DOI Open Access
Yuki Matsushita, Hayato Nakagawa, Kazuhiko Koike

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(3), P. 474 - 474

Published: Jan. 26, 2021

Lipids in our body, which are mainly composed of fatty acids, triacylglycerides, sphingolipids, phospholipids, and cholesterol, play important roles at the cellular level. In addition to being energy sources structural components biological membranes, several types lipids serve as signaling molecules or secondary messengers. Metabolic reprogramming has been recognized a hallmark cancer, but changes lipid metabolism cancer have received less attention compared glucose glutamine metabolism. However, recent innovations mass spectrometry- chromatography-based lipidomics technologies increased understanding role cancer. Changes metabolism, so-called “lipid metabolic reprogramming”, can affect functions including cell cycle, proliferation, growth, differentiation, leading carcinogenesis. Moreover, interactions between cells adjacent immune through altered known support tumor growth progression. Characterization cancer-specific be used identify novel targets for treatment, indeed, clinical trials currently underway. Thus, we discuss latest findings on biology introduce current advances technologies, focusing their applications research.

Language: Английский

Citations

73
CRISPR screens identify cholesterol biosynthesis as a therapeutic target on stemness and drug resistance of colon cancer DOI Creative Commons

Shanshan Gao,

Fraser Soares, Shiyan Wang

et al.

Oncogene, Journal Year: 2021, Volume and Issue: 40(48), P. 6601 - 6613

Published: Oct. 7, 2021

Abstract Cancer stem cells (CSCs) are responsible for tumor progression, recurrence, and drug resistance. To identify genetic vulnerabilities of colon cancer, we performed targeted CRISPR dropout screens comprising 657 Drugbank targets 317 epigenetic regulators on two patient-derived CSC-enriched spheroids. Next-generation sequencing pooled genomic DNAs isolated from surviving yielded therapeutic candidates. We unraveled 44 essential genes spheroids propagation, including key cholesterol biosynthetic (HMGCR, FDPS, GGPS1). Cholesterol biosynthesis was induced in cancer tissues, especially The pharmacological inhibition HMGCR/FDPS impaired self-renewal capacity tumorigenic potential the spheroid models vitro vivo. Mechanistically, HMGCR or FDPS depletion stemness characteristics by activating TGF-β signaling, which turn downregulated expression inhibitors differentiation (ID) proteins, stemness. geranylgeranyl diphosphate (GGPP) rescued growth inhibitory signaling effect blockade, implying a direct role these metabolites modulating Finally, 5-FU demonstrated antitumor synergy spheroids, organoids, xenografts. Taken together, our study unravels novel suggests as target conjunction with traditional chemotherapy treatment.

Language: Английский

Citations

70
Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11 DOI Creative Commons

Duanfeng Jiang,

Xin Wu,

Xiaoying Sun

et al.

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Jan. 10, 2022

Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem- and progenitor-cell origin. AML features massive proliferation abnormal blasts cells in the bone marrow inhibition normal hematopoiesis at onset. Exosomes containing proteins or nucleic acids are secreted by cells; they participate intercellular communication serve as key modulators hematopoiesis. The purpose this study was to investigate effects exosomes derived from mesenchymal stem (BMSCs) on regulation underlying mechanisms mediated microRNA (miRNA).Dysregulated miR-7-5p patients identified using qRT-PCR its clinical significance explored. Bioinformatic analysis revealed target gene OSBPL11 that could be regulated miR-7-5p. findings were validated dual-luciferase reporter assay western blotting. functional genes PI3K/AKT/mTOR signaling pathway identified, determined recovery assay. co-cultured with originating BMSCs overexpressing determine cell-cell Exo-miR-7-5p, well vitro vivo validation via gain- loss-of-function methods.Expression decreased cells. Overexpression curbed cellular promoted apoptosis. reversed tumorigenic properties vitro. Exo-miR-7-5p induced formation prone apoptosis low survival rate, expression inhibited through pathway. exhibited tumor homing vivo, development.Exo-miR-7-5p negatively regulates suppressing phosphorylation pathway, thereby inhibiting promoting data will inform development therapies based BMSC-derived exosomes.

Language: Английский

Citations

58
Dysregulation of cholesterol metabolism in cancer progression DOI
Xuesong Liu, Mengzhu Lv, Weimin Zhang

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(45), P. 3289 - 3302

Published: Sept. 29, 2023

Language: Английский

Citations

32
New insights into the therapeutic potentials of statins in cancer DOI Creative Commons
Chengyu Liu, Hong Chen, Bicheng Hu

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: July 7, 2023

The widespread clinical use of statins has contributed to significant reductions cardiovascular morbidity and mortality. Increasing preclinical epidemiological evidences have revealed that dyslipidemia is an important risk factor for carcinogenesis, invasion metastasis, as powerful inhibitor HMG-CoA reductase can exert prevention intervention effects on cancers, promote sensitivity anti-cancer drugs. mechanisms include not only inhibition cholesterol biosynthesis, but also their pleiotropic in modulating angiogenesis, apoptosis, autophagy, tumor microenvironment. Moreover, recent studies provided growing insights into the therapeutic potentials feasibility combining with other agents. Here, we provide updated review application potential cancer treatment summarize underneath mechanisms, focuses data from studies.

Language: Английский

Citations

27
Lymphatic-derived oxysterols promote anti-tumor immunity and response to immunotherapy in melanoma DOI Creative Commons

Mengzhu Sun,

Laure Garnier, Robert L. Chevalier

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 31, 2025

Language: Английский

Citations

1
Dietary Lipids Modulate Notch Signaling and Influence Adult Intestinal Development and Metabolism in Drosophila DOI Creative Commons
Rebecca Obniski, Matthew Sieber, Allan C. Spradling

et al.

Developmental Cell, Journal Year: 2018, Volume and Issue: 47(1), P. 98 - 111.e5

Published: Sept. 13, 2018

Language: Английский

Citations

77