Many types of cancer cells present constitutively activated ER stress pathways because of their significant burden of misfolded proteins coded by mutated and rearranged genes. Further increase of ER stress by pharmacological intervention may shift the balance towards cell death and can be exploited therapeutically. Recent studies have shown that an important component in the mechanism of action of mitotane, the only approved drug for the medical treatment of adrenocortical carcinoma (ACC), is represented by activation of ER stress through inhibition of the SOAT1 enzyme and accumulation of toxic lipids. Here we show that HA15, a novel inhibitor of the essential ER chaperone GRP78/BiP, inhibits ACC H295R cell proliferation and steroidogenesis and is able to synergize with mitotane action. These results suggest that convergent activation of ER stress pathways by drugs acting via different mechanisms represents a valuable therapeutic option for ACC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.mce.2018.02.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SERT-Deficient Mice Fed Western Diet Reveal Altered Metabolic and Pro-Inflammatory Responses of the Liver: A Link to Abnormal Behaviors.
Front Biosci (Landmark Ed)
January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
View Article and Find Full Text PDFOxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder.
Front Biosci (Landmark Ed)
January 2025
HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary.
Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders.
View Article and Find Full Text PDFWinery By-Products and Effects on Atherothrombotic Markers: Focus on Platelet-Activating Factor.
Front Biosci (Landmark Ed)
January 2025
Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, 17676 Athens, Greece.
Platelet aggregation and inflammation play a crucial role in atherothrombosis. Wine contains micro-constituents of proper quality and quantity that exert cardioprotective actions, partly through inhibiting platelet-activating factor (PAF), a potent inflammatory and thrombotic lipid mediator. However, wine cannot be consumed extensively due to the presence of ethanol.
View Article and Find Full Text PDFA novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway.
Pharm Biol
December 2025
The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China.
Context: The decline in ovarian reserve is a major concern in female reproductive health, often associated with oxidative stress and mitochondrial dysfunction. Although ginsenoside Rg1 is known to modulate mitophagy, its effectiveness in mitigating ovarian reserve decline remains unclear.
Objective: To investigate the role of ginsenoside Rg1 in promoting mitophagy to preserve ovarian reserve.
Neural Correlates of Social Touch Processing: An fMRI Study on Brain Functional Connectivity.
J Integr Neurosci
January 2025
Laboratory for the Study of Tactile Communication, Pushkin State Russian Language Institute, 117485 Moscow, Russia.
Background: The significance of tactile stimulation in human social development and personal interaction is well documented; however, the underlying cerebral processes remain under-researched. This study employed functional magnetic resonance imaging (fMRI) to investigate the neural correlates of social touch processing, with a particular focus on the functional connectivity associated with the aftereffects of touch.
Methods: A total of 27 experimental subjects were recruited for the study, all of whom underwent a 5-minute calf and foot massage prior to undergoing resting-state fMRI.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!