Anandamide‐induced endoplasmic reticulum stress and apoptosis are mediated by oxidative stress in non‐melanoma skin cancer: Receptor‐independent endocannabinoid signaling

Soliman, Eman; Dross, Rukiyah Van

doi:10.1002/mc.22429

Cited by 53 publications

(50 citation statements)

References 69 publications

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“…Concerning eCBs, they generally exert tumor-suppressive effect, based on clinical observations [272]. In vitro, AEA was demonstrated to decrease invasion and metastasis by upregulating a tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) [273] and to induce apoptosis via oxidative stress in COX-2- [274] and TRPV1-dependent manner [275]. 2-AG (20 mg/kg/day) showed similar properties in the rodent model, at the same time suppressing tumor immune-mediated surveillance [276].…”

Section: Cancermentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.

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Section: Cancermentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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“…We believe these findings could be on major importance for better understanding pathophysiology of psoriasis, because CB2 receptor activation is crucial signal for anti-oxidative and anti-inflammatory properties of endocannabinoids, due to their ability to decrease ROS as well as TNF-α, IFN-γ and other inflammatory cytokines [10]. On the other hand, enhanced CB1 receptor expression may increase oxidative stress and inflammation, which may be related to PsA as the advanced type of psoriasis [11]. It is also known that CB2 receptor expression is higher than is expression of CB1 in the immune-competent cells, which suggest that CB2 effects dominate in immune cells, including granulocytes [10].…”

Section: Discussionmentioning

confidence: 89%

“…The vitamins C [10] as well as A and E [11] in plasma were determined by the HPLC methods with spectrophotometric detection at 250 nm and 294 nm, respectively.…”

Section: Determination Of Low Molecular Antioxidantsmentioning

confidence: 99%

“…Among these, endocannabinoids and leukotriene B4 (LTB4) are known as pathophysiological activators of granulocytes [9]. Endocannabinoids are agonists of G protein-dependent cannabinoid receptors such as CB1 or CB2 and receptors belonging to the TRPVs and GRPs groups, whose activation modifies the level of ROS and pro-inflammatory mediators [10,11]. Activation of CB1 receptors stimulates the generation of ROS and TNFα, whereas CB2 and TRPV1 receptors have anti-inflammatory activity and contribute to the reduction of ROS levels [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Endocannabinoids are agonists of G protein-dependent cannabinoid receptors such as CB1 or CB2 and receptors belonging to the TRPVs and GRPs groups, whose activation modifies the level of ROS and pro-inflammatory mediators [10,11]. Activation of CB1 receptors stimulates the generation of ROS and TNFα, whereas CB2 and TRPV1 receptors have anti-inflammatory activity and contribute to the reduction of ROS levels [10,11]. Additionally, one of the main endocannabinoids, 2-AG, is directly able to impair both inflammation, as well as oxidative stress, which is often considered to be a compensatory or adaptive mechanism [12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in Granulocytes and Plasma of Psoriatic Patients

Ambrożewic¹,

Wójcik²,

Wroński³

et al. 2018

Preprint

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Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects.The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis.This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.

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Zinc chelator TPEN induces pancreatic cancer cell death through causing oxidative stress and inhibiting cell autophagy

Chen

et al. 2019

Journal Cellular Physiology

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The essential trace element zinc (Zn) is widely required in cellular functions, and abnormal Zn homeostasis causes a variety of health problems including immunodeficiency and sensory dysfunctions. Previous studies had shown that Zn availability was also important for tumor growth and progression. The aim of the present study was to investigate the potential mechanisms of N,N,N,N-Tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN) (a membrane permeable zinc chelator) induced pancreatic cancer cell death. The text of inductively coupled plasma-mass spectrometry (ICP-MS) showed in human pancreatic cancer samples that the zinc content in cancer was higher than that in adjacent tissues. The pancreatic cancer cell lines Panc-1, 8988T, BxPc-3, and L3.6 were used in this study. Our results indicated that TPEN markedly induced cell death, via increasing reactive oxygen species (ROS) and restraining autophagy. Our data also indicated that TPEN-stimulated mitochondrial metabolism produced much ROS. Meanwhile, TPEN reduced the levels of glutathione (GSH) and triggered ROS outbreak, which were the main causes of cell death.In addition, cell autophagy was significantly depressed in Panc-1 cells treated by TPEN, which was due to the ability of disrupting lysosomal by TPEN. Thus, we thought zinc depletion by TPEN was a potential therapeutic strategy for pancreatic cancer. K E Y W O R D S autophagy, lysosome, mitochondrial metabolism, ROS, TPEN

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Anandamide‐induced endoplasmic reticulum stress and apoptosis are mediated by oxidative stress in non‐melanoma skin cancer: Receptor‐independent endocannabinoid signaling

Cited by 53 publications

References 69 publications

A Guide to Targeting the Endocannabinoid System in Drug Design

A Guide to Targeting the Endocannabinoid System in Drug Design

Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in Granulocytes and Plasma of Psoriatic Patients

Zinc chelator TPEN induces pancreatic cancer cell death through causing oxidative stress and inhibiting cell autophagy

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