Comparative study of ergosterol and 7‐dehydrocholesterol and their endoperoxides: Generation, identification, and impact in phospholipid membranes and melanoma cells DOI Open Access
Megumi Nishitani Yukuyama,

Karen Campos Fabiano,

Alex Inague

et al.

Photochemistry and Photobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Abstract Melanoma is an aggressive cancer that has attracted attention in recent years due to its high mortality rate of 80%. Damage caused by oxidative stress generated radical (type I reaction) and singlet oxygen, 1 O 2 II reactions may induce cancer. Thus, studies aim unveil the mechanism drives these damage processes become relevant. Ergosterol, analogue 7‐dehydrocholesterol, important structure cell membranes, widely explored treatment. However, date little known about impact different on sterols melanoma treatment, conflicting results their effectiveness complicates understanding role damage. Our highlight differences among ergosterol, 7‐dehydrocholesterol (7‐DHC), cholesterol membrane properties when subjected distinct reactions. Furthermore, we conducted a comparative study exploring mechanisms photodynamic treatment A375 melanoma. Notably, endoperoxides from ergosterol 7‐DHC showed superior efficacy reducing viability cells compared precursor molecules. We also describe step‐by‐step process produce identify derived 7‐DHC. While further are needed, this work provides new insights for death induced presence biologically relevant sterols.

Language: Английский

Glioblastoma-derived exosomes promote lipid accumulation and induce ferroptosis in dendritic cells via the NRF2/GPX4 pathway DOI Creative Commons
Jian Yang, Mingqi Zhang, Xuying Zhang

et al.

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

Published: Aug. 13, 2024

Glioblastoma-derived exosomes (GDEs), containing nucleic acids, proteins, fatty acids and other substances, perform multiple important functions in glioblastoma microenvironment. Tumor-derived serve as carriers of induce a shift metabolism towards oxidative phosphorylation, thus driving immune dysfunction dendritic cells (DCs). Lipid peroxidation is an characteristic ferroptosis. Nevertheless, it remains unclear whether GDEs can lipid accumulation oxidation to trigger ferroptosis DCs. In our study, we investigate the impact on DCs by inhibiting secretion through knocking down expression Rab27a using rat orthotopic model. The results show that reduce infiltrating brain decrease mature (mDCs) levels, thereby suppressing growth. Mechanistically, employed vitro treatments bone marrow-derived (BMDCs) with GDEs. indicate viability mDCs compared immature (imDCs) via NRF2/GPX4 pathway. Overall, these findings provide new insights into development immune-suppressive microenvironment interaction

Language: Английский

Citations

10
Specific activity of mouse liver desaturases and elongases: Time course effects using n-3 and n-6 PUFA substrates and inhibitory responses of delta-6 desaturase DOI
Rodrigo Valenzuela,

Adam H. Metherel,

Giulia Cisbani

et al.

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2025, Volume and Issue: 1870(2), P. 159594 - 159594

Published: Jan. 10, 2025

Language: Английский

Citations

1
Epithelial-mesenchymal Transition Promotes Metabolic Reprogramming to Suppress Ferroptosis DOI
Wenzheng Guo, Zhibing Duan, Jingjing Wu

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
ER remodeling via lipid metabolism DOI Creative Commons
Wonyul Jang, Volker Haucke

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(11), P. 942 - 954

Published: Feb. 23, 2024

Unlike most other organelles found in multiple copies, the endoplasmic reticulum (ER) is a unique singular organelle within eukaryotic cells. Despite its continuous membrane structure, encompassing more than half of cellular endomembrane system, ER subdivided into specialized sub-compartments, including morphological, contact site (MCS), and de novo biogenesis domains. In this review, we discuss recent emerging evidence indicating that, response to nutrient stress, cells undergo reorganization these sub-compartmental domains through two main mechanisms: non-destructive remodeling morphological via regulation MCS hitchhiking, destructive by ER-phagy. We further highlight propose critical role lipid metabolism during starvation.

Language: Английский

Citations

8
Starvation-resistant cavefish reveal conserved mechanisms of starvation-induced hepatic lipotoxicity DOI Creative Commons
Macarena Pozo‐Morales, Ansa E. Cobham, Cielo Centola

et al.

Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(5), P. e202302458 - e202302458

Published: March 11, 2024

Starvation causes the accumulation of lipid droplets in liver, a somewhat counterintuitive phenomenon that is nevertheless conserved from flies to humans. Much like fatty liver resulting overfeeding, hepatic (steatosis) during undernourishment can lead lipotoxicity and atrophy liver. Here, we found although surface populations Astyanax mexicanus undergo this evolutionarily response starvation, starvation-resistant cavefish larvae same species do not display an upon starvation. Moreover, are resistant providing unique system explore strategies for protection. Using comparative transcriptomics between zebrafish, fish, cavefish, identified acid transporter slc27a2a/fatp2 be correlated with development Pharmacological inhibition slc27a2a zebrafish rescues steatosis Furthermore, down-regulation FATP2 Drosophila inhibits starvation-induced steatosis, suggesting importance gene regulating nutrition deprivation. Overall, our study identifies conserved, druggable target protect

Language: Английский

Citations

7
Targeting ALDH1A1 to enhance the efficacy of KRAS-targeted therapy through ferroptosis DOI Creative Commons
Yunyi Bian, Guangyao Shan, Guoshu Bi

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 77, P. 103361 - 103361

Published: Sept. 20, 2024

KRAS is among the most commonly mutated oncogenes in human malignancies. Although advent of sotorasib and adagrasib, has lifted "undruggable" stigma KRAS, resistance to inhibitors quickly becomes a major issue. Here, we reported that aldehyde dehydrogenase 1 family member A1 (ALDH1A1), an enzyme retinoic acid biosynthesis redox balance, increases response confers range cancer types. inhibitors' efficacy significantly improved sensitive or drug-resistant cells, patient-derived organoids (PDO), xenograft models by ALDH1A1 knockout, loss function, inhibitor. Furthermore, discovered suppresses counteracting ferroptosis. detoxicates deleterious aldehydes, boosts synthesis NADH (RA), improves RARA function. also activates CREB1/GPX4 pathway, stimulates production lipid droplets pH-dependent manner, subsequently prevents ferroptosis induced inhibitors. Meanwhile, established GTF2I dephosphorylated at S784 via ERK inhibitors, which hinders its nuclear translocation mediates ALDH1A1's upregulation In summary, results offer valuable insights into targeting enhance effectiveness KRAS-targeted therapy through treatment.

Language: Английский

Citations

7
Concentration-dependent dual roles of proanthocyanidins on oxidative stress and docosahexaenoic acid production in Schizochytrium sp. ATCC 20888 DOI

Guofu Zhao,

Ming Chen, Jingwen Liu

et al.

Bioresource Technology, Journal Year: 2024, Volume and Issue: 398, P. 130537 - 130537

Published: March 5, 2024

Language: Английский

Citations

6
The Lipidomic Signature of Glioblastoma: A Promising Frontier in Cancer Research DOI Open Access
Nina Yu, Orwa Aboud

Cancers, Journal Year: 2024, Volume and Issue: 16(6), P. 1089 - 1089

Published: March 8, 2024

Glioblastoma is the most aggressive primary brain malignancy in adults, and has a survival duration of approximately 15 months. First line treatment involves surgical resection, chemotherapy, radiation, but despite multi-pronged approach advances cancer research, glioblastoma remains devastating with high mortality rate. Lipidomics an emerging discipline that studies lipid pathways characteristics, promising field to understand biochemical mechanisms. In glioblastoma, disrupted homeostasis been reported literature. A thorough understanding serum lipidomics may offer ways better biomarkers, prognosis, options. Here, we review literature, offering future directions for research glioblastomas.

Language: Английский

Citations

6
NFE2L2 and ferroptosis resistance in cancer therapy DOI Open Access
Daolin Tang, Rui Kang

Cancer Drug Resistance, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

NFE2-like basic leucine zipper transcription factor 2 (NFE2L2, also known as NRF2), is a key in the cellular defense against oxidative stress, playing crucial role cancer cell survival and resistance to therapies. This review outlines current knowledge on link between NFE2L2 ferroptosis - form of regulated death characterized by iron-dependent lipid peroxidation within cells. While activation can protect normal cells from damage, its overexpression contributes drug upregulating antioxidant defenses inhibiting ferroptosis. We delve into molecular pathways ferroptosis, highlighting involvement target genes, such

Language: Английский

Citations

6
Prostate Cancer and the Mevalonate Pathway DOI Open Access
Patricia Guerrero-Ochoa, Sergio Rodríguez-Zapater, Alberto Anel

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2152 - 2152

Published: Feb. 10, 2024

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to emergence of resistance mechanisms tumor employs when subjected monomolecular treatments. This review illustrates how dysregulation lipid metabolic pathway constitutes survival strategy adopted by tumors evade eradication efforts. Integrating this aspect into oncological management could prove valuable combating PCa.

Language: Английский

Citations

5