Prostate Cancer and the Mevalonate Pathway

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

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Cancer cells employ lipid droplets to survive toxic stress

The Prostate, Journal Year: 2024, Volume and Issue: 84(7), P. 644 - 655

Published: Feb. 26, 2024

Abstract Background Lipid reprogramming is a known mechanism to increase the energetic demands of proliferating cancer cells drive and support tumorigenesis progression. Elevated lipid droplets (LDs) are well‐known alteration in many cancers, including prostate (PCa), associated with high tumor aggressiveness as well therapy resistance. The LD accumulation specific functions still not understood; however, it has been shown that LDs can form protective against lipotoxicity peroxidation cell. Methods This study investigated significance PCa. was done by staining, imaging, image quantification, flow cytometry analysis PCa cells. Additionally, lipidomics metabolomics experiments were performed assess difference metabolites lipids control treatment surviving Lastly, clinical significance, multiple publicly available datasets mined for LD‐related data. Results Our demonstrated breast survive 72 h chemotherapy have elevated LDs. These formed tandem reactive oxygen species levels sequester damaged excess created oxidative stress, which promoted cell survival. inhibiting diacylglycerol O ‐acyltransferase 1 (DGAT1) (which catalyzes triglyceride synthesis into LDs) treating simultaneously, we able decrease overall amount death compared alone. Conclusions Overall, our proposes potential combination DGAT1 inhibitors death.

Language: Английский

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CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 8, 2024

Abstract Imbalances in lipid storage and secretion lead to the accumulation of hepatocyte droplets (LDs) (i.e., hepatic steatosis). Our understanding mechanisms that govern channeling neutral lipids towards cytosolic LDs or secreted lipoproteins remains incomplete. Here, we performed a series CRISPR-Cas9 screens under different metabolic states uncover flux. Clustering chemical-genetic interactions identified CLIC-like chloride channel 1 (CLCC1) as critical regulator secretion. Loss CLCC1 resulted buildup large hepatoma cells knockout mice caused liver steatosis. Remarkably, are lumen ER exhibit properties lipoproteins, indicating profound shift Finally, remote homology searches domain is homologous yeast Brl1p Brr6p, factors promote fusion inner outer nuclear envelopes during pore complex assembly. extensive membrane herniations, consistent with impaired Thus, identify human Brl1p/Brr6p homolog propose CLCC1-mediated remodeling promotes flux

Language: Английский

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Deeper insight into ferroptosis: association with Alzheimer’s, Parkinson’s disease, and brain tumors and their possible treatment by nanomaterials induced ferroptosis

Redox Report, Journal Year: 2023, Volume and Issue: 28(1)

Published: Nov. 27, 2023

Ferroptosis is an emerging and novel type of iron-dependent programmed cell death which mainly caused by the excessive deposition free intracellular iron in brain cells. This deposited exerts a ferroptosis pathway, resulting lipid peroxidation (LiPr). There are three pathways viz. metabolism-mediated cysteine/glutamate, LiPr-mediated. Iron required as redox metal for several physiological activities. Due to homeostasis balance disruption, gets adversely affected further causes neurodegenerative diseases (NDDs) like Parkinson's Alzheimer's disease, strokes, tumors glioblastoma (GBS), glioma. Nanotechnology has played important role prevention treatment these NDDs. A synergistic effect nanomaterials could prove be effective efficient approach field nanomedicine. In current review, authors have highlighted all latest research ferroptosis, specifically emphasizing on major molecular key players various mechanisms involved pathway. Moreover, here also addressed correlation with pathophysiology NDDs theragnostic

Language: Английский

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Endoplasmic Reticulum Stress and Obesity

Advances in experimental medicine and biology, Journal Year: 2024, Volume and Issue: unknown, P. 373 - 390

Published: Jan. 1, 2024

Language: Английский

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