Cellular battle against endoplasmic reticulum stress and its adverse effect on health

Divya, S.; Ravanan, Palaniyandi

doi:10.1016/j.lfs.2023.121705

Cited by 8 publications

(2 citation statements)

References 151 publications

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“…Our study notably reveals that Morus alba L. compounds induce significant ER stress and UPR in cancer cells. While the UPR typically acts as a cell's defense mechanism, ensuring cellular protein homeostasis [116], it can also initiate cell death when the damage is too extensive [117]. Recent insights suggest leveraging this UPR activation as a cancer treatment strategy [118], given that cancer cells, already stressed, might be especially vulnerable to agents that amplify this stress.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran

Zhang,

Hu,

et al. 2024

IJMS

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Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3′-Geranyl-3-prenyl-5,7,2′,4′-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate significant anti-cancer properties against various gastrointestinal cancers, including colon, pancreatic, and gastric cancers. The anti-cancer mechanism of these chemical components was explored in gastric cancer cells, revealing that they inhibit cell cycle and DNA replication-related gene expression, leading to the effective suppression of tumor cell growth. Additionally, they induced unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, potentially resulting in DNA damage, autophagy, and cell death. Moracin P, an active monomer characterized as a 2-arylbenzofuran, was found to induce ER stress and promote apoptosis in gastric cancer cells, confirming its potential to inhibit tumor cell growth in vitro and in vivo. These findings highlight the therapeutic potential of Morus alba L. monomers in gastrointestinal cancers, especially focusing on Moracin P as a potent inducer of ER stress and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran

Zhang,

Hu,

et al. 2024

IJMS

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“…Peroxisomal metabolism and oxidative stress are closely linked and have been implicated in various human diseases [12]. Furthermore, the endoplasmic reticulum (ER) is another cellular source for ROS due to alterations in ER-regulated protein folding pathways [13]. Several studies have implicated redox imbalance, oxidative stress, and depletion of GSH in many pathological conditions, where unresolved cellular damage caused by the effects of ROS can result in cell death or drive the development of various diseases, including rare diseases-and treating this imbalance using an agent such as NAC can be beneficial [9,14].…”

Section: Introductionmentioning

confidence: 99%

N-acetylcysteine Pharmacology and Applications in Rare Diseases—Repurposing an Old Antioxidant

2023

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N-acetylcysteine (NAC), a precursor of cysteine and, thereby, glutathione (GSH), acts as an antioxidant through a variety of mechanisms, including oxidant scavenging, GSH replenishment, antioxidant signaling, etc. Owing to the variety of proposed targets, NAC has a long history of use as a prescription product and in wide-ranging applications that are off-label as an over-the-counter (OTC) product. Despite its discovery in the early 1960s and its development for various indications, systematic clinical pharmacology explorations of NAC pharmacokinetics (PK), pharmacodynamic targets, drug interactions, and dose-ranging are sorely limited. Although there are anecdotal instances of NAC benefits in a variety of diseases, a comprehensive review of the use of NAC in rare diseases does not exist. In this review, we attempt to summarize the existing literature focused on NAC explorations in rare diseases targeting mitochondrial dysfunction along with the history of NAC usage, approved indications, mechanisms of action, safety, and PK characterization. Further, we introduce the research currently underway on other structural derivatives of NAC and acknowledge the continuum of efforts through pre-clinical and clinical research to facilitate further therapeutic development of NAC or its derivatives for rare diseases.

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The potential protective role of carotenoids from saffron: A focus on endoplasmic reticulum stress‐related organ damage

Mirzavi,

Rajabian,

Hosseini

2024

Food Science & Nutrition

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The anticancer, antioxidant, and immunomodulatory properties of carotenoids from saffron or apocarotenoids (e.g., crocin, safranal, crocetin, and picrocrocin) have prompted research into their benefits. Apocarotenoids seem to be effective compound for the treatment of chronic diseases, such as neurodegenerative, cardiovascular, cancer, respiratory, and metabolic disorders. Endoplasmic reticulum (ER) is an essential organelle found in the cytoplasm of eukaryotic cells that participates in the biosynthesis of proteins, lipids, and steroid hormones. Given the role of the ER in the regulation of several fundamental biological processes, including metabolic pathways and immune responses, aberrant ER function can have a significant influence on these vital processes and result in serious pathological consequences. Exposure of cell to adverse environmental challenges, such as toxic agents, ischemia, and so on, causes accumulation of unfolded or misfolded proteins in the ER lumen, also called ER stress. There is a growing evidence to suggest that ER disturbance in the form of oxidative/nitrosative stress and subsequent apoptotic cell death plays major roles in the pathogenesis of many human diseases, including cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, and liver diseases. Apocarotenoids with their unique properties can modulate ER stress through PERK/eIF2α/ATF4/CHOP (protein kinase R (PKR)‐like ER kinase/eukaryotic initiation factor 2α/activating transcription factor 4/C/EBP /homologous protein) and X‐Box Binding Protein 1/activating transcription factor 6 (XBP1/ATF6) pathways. In addition, they suppress apoptosis through inhibition of endoplasmic and mitochondrial‐dependent caspase cascade and can stimulate SIRT1 (silent information regulator 1) and Nrf2 (nuclear factor erythroid 2‐related factor 2) expression, thereby leading to protection against oxidative stress. This review summarizes the potential benefits of apocarotenoids in various ER‐stress‐related disorders.

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Cellular battle against endoplasmic reticulum stress and its adverse effect on health

Cited by 8 publications

References 151 publications

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran

N-acetylcysteine Pharmacology and Applications in Rare Diseases—Repurposing an Old Antioxidant

The potential protective role of carotenoids from saffron: A focus on endoplasmic reticulum stress‐related organ damage

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