Mitochondrial calcium overload contributes to cannabinoid‐induced paraptosis in hormone‐responsive breast cancer cells

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(10)

Published: May 9, 2024

Abstract Studies have shown that natural products can induce paraptosis in tumour cell lines. Paraptosis is characterized by cytoplasmic vacuolation arising from the endoplasmic reticulum (ER) and mitochondria. The mechanism of unclear; however, dysregulation Ca 2+ homeostasis believed to affect induction. This study investigated death induced a phytocannabinoid ratio MCF7 breast cancer line. crystal violet assay was used detect changes viability morphology were using light transmission electron microscopy. Various inhibitors, fluorescent staining with high‐content screening, Western blot analysis investigate different mechanisms. significant cells; no apoptosis, necrosis, autophagy, or ferroptosis detected. Vacuolation treatment inhibited cycloheximide, suggesting induction investigated, it found (1) ER dilation mitochondrial swelling, (2) stress overload dysfunction, which appeared be mediated voltage‐dependent anion channel, (3) significantly impaired all metabolic pathways. data demonstrated cannabinoid flux These findings highlight novel cannabinoid‐induced emphasize anti‐cancer potential ratios, exhibited enhanced effects compared individual cannabinoids.

Language: Английский

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Potential Roles of IP3 Receptors and Calcium in Programmed Cell Death and Implications in Cardiovascular Diseases

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1334 - 1334

Published: Oct. 20, 2024

Inositol 1,4,5-trisphosphate receptors (IP

Language: Английский

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Therapeutic approaches targeting aging and cellular senescence in Huntington's disease

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(10)

Published: Oct. 1, 2024

Huntington's disease (HD) is a devastating neurodegenerative that manifested by gradual loss of physical, cognitive, and mental abilities. As the advances, age has major impact on pathogenic signature mutant huntingtin (mHTT) protein aggregation. This review aims to explore intricate relationship between aging, mHTT toxicity, cellular senescence in HD. Scientific data interplay mHTT, HD were collected from several academic databases, including PubMed, Google Scholar, Google, ScienceDirect. The search terms employed "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," "CELLULAR SENESCENCE." Additionally, gather information molecular mechanisms potential therapeutic targets, was extended include relevant such as "DNA DAMAGE," "OXIDATIVE STRESS," "AUTOPHAGY." According research, aging leads worsening pathophysiology through some processes. result accumulation, promoted, which causes DNA damage, oxidative stress, decreased autophagy, increased inflammatory responses. Pro-inflammatory cytokines other substances are released senescent cells, may worsen neuronal damage course disease. It been shown treatments directed at these pathways reduce symptoms enhance longevity experimental animals, pointing new possibility treating condition. Through their amplification harmful effects play crucial roles development Comprehending interplays creates novel opportunities for measures targeted alleviating enhancing patients' quality life.

Language: Английский

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Glutathione restores the mitochondrial redox status and improves the function of the cardiovascular system in old rats

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 9, 2023

Introduction: Aging is accompanied by cardiovascular disorders which associated with an imbalance of pro- and antioxidant systems, the mitochondrial dysfunction, etc. Glutathione (GSH) plays a critical role in protecting cells from oxidative damage. The aim work was to study effect exogenous glutathione on redox status mitochondria, content H 2 S function system old rats. Methods: Experiments were performed adult (6 months) (24 Wistar rats divided into three groups: adult, glutathionetreated injected intraperitoneally at dose 52 mg/kg. We investigated balance, levels, stress, opening permeability transition pore (mPTP), resistance isolated heart ischemia/reperfusion Langendorff model, endothelium-dependent vasorelaxation aortic rings, cardiac levels 3-MST , CSE UCP3 mRNA determined using real-time PCR analysis. Results: Our data shows that treated glutathione, balance its oxidized reduced form changes direction significant increase (by 53.6%) form. pretreatment significantly increased mtNOS activity, expression considered as protective protein, conversely, decreased stress markers (the rate O • − generation, diene conjugates malone dialdehyde, 2.5, 2.3, 2, 1.6 times, respectively) mitochondria. This inhibition these animals. At same time, glutathione-treated rats, we also observed restoration responses acetylcholine, almost completely abolished NO-synthase inhibitor L-NAME. Conclusion: Thus, restores improves system.

Language: Английский

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Hybrid non-animal modeling: A mechanistic approach to predict chemical hepatotoxicity

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 471, P. 134297 - 134297

Published: April 12, 2024

Language: Английский

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