Tanshinone IIA acts as a regulator of lipogenesis to overcome osimertinib acquired resistance in lung cancer

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 224, P. 116207 - 116207

Published: April 25, 2024

Language: Английский

---

Taoyuan Decoction Improved Metrnl Insufficiency Causing Accentuation of Myocardial Infarction-Induced Cardiac Remodeling and Myocardial Energy Metabolism Dysfunction Through Ampk-Mediated Fatty Acid Oxidation

Published: Jan. 1, 2025

Background: Heart failure (HF) represents the terminal stage of various cardiovascular diseases, including myocardial infarction (MI), with energy metabolism playing a crucial role in its progression. Fatty acid oxidation (FAO) constitutes primary pathway metabolism, providing 60%-90% cardiac through FAO. However, precise mechanisms regulating this process remain elusive.Methods: In study, we investigated Meteorin-like protein (Metrnl) MI-induced remodeling and dysfunction using rat models left coronary artery ligation H9c2 cardiomyocytes.Results: Our findings revealed decreased Metrnl expression serum HF patients rats, accompanied by alterations AMPK other lipid indicators. knockdown cardiomyocytes exacerbated remodeling, dysfunction, disorders. Taoyuan decoction (TYD), widely used clinically as an effective alternative treatment for heart failure, was found to enhance FAO, ameliorate mitochondrial improve thereby ensuring adequate supply promoting function rats.Conclusion: These suggest that targeting Metrnl/AMPK axis promising therapeutic strategy post-MI failure.

Language: Английский

---

Prostate cancer cells elevate glycolysis and G6PD in response to caffeic acid phenethyl ester-induced growth inhibition

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 16, 2025

Caffeic acid phenethyl ester (CAPE) is the main bioactive component of poplar type propolis. We previously reported that treatment with caffeic suppressed cell proliferation, tumor growth, as well migration and invasion prostate cancer (PCa) cells via inhibition signaling pathways AKT, c-Myc, Wnt EGFR. also demonstrated combined CAPE docetaxel altered genes involved in glycolysis tricarboxylic (TCA) cycle. therefore suspect may interfere glucose metabolism PCa cells. Seahorse Bioenergetics platform was applied to analyzed extra cellular acidification rate (ECAR) oxygen consumption (OCR) under treatment. UPLC-MSMS Multiple Reaction Monitoring (MRM), PCR, western blot were used analyze effects on metabolites, genes, proteins glycolysis, TCA cycle pentose phosphate pathway Flow cytometry ELISA determine level reactive species being treated CAPE. analysis revealed ECAR, OCR, ATP production elevated C4-2B Protein levels glucose-6-phosphate dehydrogenase (G6PD), phosphogluconate (PGD), glutaminase (GLS), phospho-AMPK Thr172 abundance pyruvate, lactate, ribulose-5-phosphate, sedoheptulose-7-phosphate increased CAPE-treated ROS decreased 48 h after Co-treatment AMPK inhibitor exhibited additive growth Our study indicated attempted overcome CAPE-induced stress by upregulation G6PD but failed impede caused Concurrent inhibitors targeting be effective therapy for advanced PCa.

Language: Английский

---

S‐Methyl Methanethiosulfonate, the Main Human Metabolite of S‐Methyl‐L‐Cysteine Sulfoxide, Alters Energy Metabolism in Prostate Cancer Cells

Molecular Nutrition & Food Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

Cruciferous and allium vegetables contain the sulfur compound S-methyl-L-cysteine-sulfoxide (SMCSO). Considering SMCSO is found at a higher abundance compared to glucosinolates, there are limited reports on its effect health, with majority of evidence beneficial effects glucose metabolism in rodent models. In current study, we investigated metabolic metabolite, S-methyl methanethiosulfonate (MMTSO), prostate cancer metabolism. DU145 cells were cultured 5.5 mM (basal), 10 (intermediate) 25 (high) concentrations presence or MMTSO (100 µM). Using Seahorse technology, but not reduced mitochondrial metabolism, ATP, percentage oxidative phosphorylation increased fatty acid dependency cells. Transcriptomic metabolomic analyses observed cellular energy pathways immune response changes. These data show that alters several features cells, shifting them towards non-cancerous phenotype. consistent notion may contribute broccoli-rich diet cancer.

Language: Английский

---

Role of genetic variants and DNA methylation of lipid metabolism-related genes in metabolic dysfunction-associated steatotic liver disease

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

Published: March 17, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD), is one of the most common chronic diseases, which encompasses a spectrum from metabolic (MASL) to steatohepatitis (MASH), and may ultimately progress MASH-related cirrhosis hepatocellular carcinoma (HCC). MASLD complex that influenced by genetic environmental factors. Dysregulation hepatic lipid metabolism plays crucial role in development progression MASLD. Therefore, focus this review discuss links between variants DNA methylation metabolism-related genes pathogenesis. We first summarize interplay disturbance metabolism. Next, we on reviewing related gene loci onset existing literature around single nucleotide polymorphisms (SNPs) associated with identified genome-wide association studies (GWAS) candidate analyses. Moreover, based recent evidence human animal studies, further discussed regulatory function mechanisms changes levels occurrence MASLD, particular emphasis its MASH. Furthermore, alterations blood MASH patients. Finally, introduce potential value profiles developing novel prognostic biomarkers therapeutic targets for intending provide references future

Language: Английский

---

Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer

Biology, Journal Year: 2025, Volume and Issue: 14(5), P. 507 - 507

Published: May 6, 2025

Prostate cancer (PCa) is not only one of the most diagnosed malignancies in men but also a leading cause cancer-related mortality globally. PCa exhibits unique metabolic dependencies, particularly on lipids and glutamine, unlike many solid tumors, rather than glycolysis. Methionine metabolism plays crucial role these pathways, contributing to polyamine biosynthesis, DNA methylation, cellular signaling processes. Here, we demonstrate that methionine deprivation induces selective vulnerability AMPK-deficient PC3 cells by disrupting SAMTOR–mTOR triggering oxidative stress, lipid depletion, autophagic responses. Through functional proteomic analyses, show SAMTOR directly interacts with p-AMPK modulates cell fate under methionine-limited conditions. Our findings establish mechanistic link between sensing stress PCa, offering new avenue for targeted intervention.

Language: Английский

---

Molecular Mechanism of Tanshinone against Prostate Cancer

Molecules, Journal Year: 2022, Volume and Issue: 27(17), P. 5594 - 5594

Published: Aug. 30, 2022

Prostate cancer (PCa) is the most common malignant tumor of male urinary system in Europe and America. According to data World Cancer Report 2020, incidence rate PCa ranks second prevalence tumors varies worldwide between regions population groups. Although early can achieve good therapeutic results after surgical treatment, due advanced PCa, it adapt tolerate androgen castration-related drugs through a variety mechanisms. For this reason, often difficult effective treatment PCa. Tanshinone new fat-soluble phenanthraquinone compound derived from Salvia miltiorrhiza that play role different cancers, including Several studies have shown target various molecular pathways signal transducer activator transcription 3 (STAT3) pathway, receptor (AR) phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian rapamycin (mTOR) mitogen-activated protein (MAPK) which will affect release pro-inflammatory cytokines cell proliferation, apoptosis, metabolism, genomic stability, drug resistance. Thus, occurrence development cells are inhibited. In review, we summarized vivo vitro evidence against prostate discussed effect on nuclear factor kappa-B (NF-κB), AR, mTOR. At same time, conducted network pharmacology analysis four main components further screen possible targets provide ideas for future research.

Language: Английский

---

Ferroptosis landscape in prostate cancer from molecular and metabolic perspective

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 15, 2023

Abstract Prostate cancer is a major disease that threatens men’s health. Its rapid progression, easy metastasis, and late castration resistance have brought obstacles to treatment. It necessary find new effective anticancer methods. Ferroptosis novel iron-dependent programmed cell death plays role in various cancers. Understanding how ferroptosis regulated prostate will help us use it as way kill cells. In this review, we summarize the regulation of relationship with AR from perspective metabolism molecular pathways. We also discuss feasibility treatment describe current limitations prospects, providing reference for future research clinical application ferroptosis.

Language: Английский

---

New insights into lipid metabolism and prostate cancer (Review)

International Journal of Oncology, Journal Year: 2023, Volume and Issue: 62(6)

Published: May 17, 2023

Prostate cancer (PCa) is the most common malignant tumor of male urological system and poses a severe threat to survival middle‑aged elderly males worldwide. The development progression PCa are affected by variety biological processes, including proliferation, apoptosis, migration, invasion maintenance membrane homeostasis cells. present review summarizes recent research advances in lipid (fatty acid, cholesterol phospholipid) metabolic pathways PCa. In first section, metabolism fatty acids highlighted, from formation catabolism associated proteins. Subsequently, role pathogenesis evolution described detail. Finally, different types phospholipids their association with also discussed. addition impact key proteins on growth, metastasis drug resistance, clinical value acids, phospholipids, as diagnostic prognostic indicators therapeutic targets

Language: Английский

---

Comprehensive analysis of stearoyl-coenzyme A desaturase in prostate adenocarcinoma: insights into gene expression, immune microenvironment and tumor progression

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 16, 2024

Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) documented regulate in multiple cancers, landscape analysis of its implications PRAD are still missing at present. Here, we conducted an diverse datasets revealing elevated SCD expression the cohort both mRNA and protein levels. Interestingly, was associated with promoter hypermethylation genetic alterations, notably L134V mutation. Integration comprehensive immunological genomic data revealed robust positive correlation between levels abundance CD8 + T cells macrophages. Further analyses identified significant associations various immune markers microenvironment. Single-cell transcriptomic profiling unveiled differential patterns across distinct cell types within prostate The Gene Ontology Kyoto Encyclopedia Genes Genome showed that enriched pathways were primarily related biosynthesis, cholesterol endoplasmic reticulum membrane functions, metabolic pathways. Set Enrichment Analysis highlighted involvement crucial cellular processes, including cycle biosynthesis cofactors In functional studies, overexpression promoted proliferation, metastasis invasion cells, whereas downregulation inhibits these processes. This study provides insights into multifaceted roles pathogenesis, underscoring potential as therapeutic target prognostic biomarker.

Language: Английский

---