Exploring the Therapeutic Potential of Cannabidiol in U87MG Cells: Effects on Autophagy and NRF2 Pathway DOI Creative Commons
Laura Giannotti, Benedetta Di Chiara Stanca, Francesco Spedicato

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 14(1), P. 18 - 18

Published: Dec. 26, 2024

Cannabinoids include both endogenous endocannabinoids and exogenous phytocannabinoids, such as cannabidiol (CBD), have potential therapeutic agents in cancer treatment due to their selective anticancer activities. CBD exhibits antioxidant pro-oxidant effects depending on its concentration cell types. These properties allow influence oxidative stress responses potentially enhance the efficacy of antitumor therapies. In this study, we treated U87MG glioma cells with low dose (1 μM) evaluated molecular effects. Our findings indicate that reduced viability by 20% (p < 0.05) through alteration mitochondrial membrane potential. The redox status caused an attempt rescue functionality nuclear localization GABP transcription factor involved mitochondria biogenesis. Moreover, increase autophagic flux, supported Beclin-1 ratio LC3-II/LC3-I. Due alteration, pro-apoptotic proteins were induced without activating apoptotic effectors Caspase-3 or Caspase-7. study NRF2 ubiquitin-binding protein p62 expression revealed levels CBD-treated cells. conclusion, low-dose makes more vulnerable cytotoxic effects, reducing dynamics while increasing flux systems. This explains mechanisms which respond treatment. highlight CBD, suggesting modulating autophagy pathways could represent a promising strategy for glioblastoma

Language: Английский

New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy DOI Creative Commons
Aleksandra Majchrzak‐Celińska, Elżbieta Studzińska-Sroka

Molecules, Journal Year: 2024, Volume and Issue: 29(7), P. 1682 - 1682

Published: April 8, 2024

Phytocompounds have been evaluated for their anti-glioblastoma actions decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy the vitro studies, poor bioavailability, low tumor accumulation, and rapid clearance compromise vivo. Here, we present new avenues phytocompound research improvement of glioblastoma therapy, including ways to enhance response temozolomide using phytochemicals, current focus on phytocompound-based immunotherapy, or use phytocompounds as photosensitizers photodynamic therapy. Moreover, new, intensively approaches, such chemical modifications phytochemicals encapsulation numerous types nanoformulations, improve bioavailability delivery brain. Finally, clinical trials evaluating role phytocompound-derived drugs therapy less studied plant extracts that recently found possess properties. Overall, recent advancements are encouraging; however, more 3D models, vivo it is possible upgrade treatment a satisfactory level.

Language: Английский

Citations

2
Endocannabinoid system and phytocannabinoids in the main species of veterinary interest: a comparative review DOI Creative Commons
Alessandra Di Salvo, Elisabetta Chiaradia, Monica Sforna

et al.

Veterinary Research Communications, Journal Year: 2024, Volume and Issue: 48(5), P. 2915 - 2941

Published: Aug. 20, 2024

Since the discovery of endocannabinoid system and due to empirical evidence therapeutic effects on several illnesses both in humans animals that follow administration exogenous cannabinoids (i.e., phytocannabinoids), numerous studies have been conducted. These investigations aimed identify expression distribution cannabinoid receptors healthy pathologic organs tissues different animal species define interactions phytocannabinoids with these receptors. In last decade, pharmacokinetics, efficacy tolerability many Cannabis derivatives formulations, mainly containing cannabidiol, main veterinary interest, also investigated. This manuscript summarizes findings reported by scientific published so far molecular mode action phytocannabinoids, localization tissues, as well dogs, cats, horses other interest. A deep knowledge issues is crucial for use purposes species.

Language: Английский

Citations

2
Delta-9-Tetrahydrocannabinol Blocks Bone Marrow-Derived Macrophage Differentiation through Elimination of Reactive Oxygen Species DOI Creative Commons

Taylor H. Carter,

Chloe E. Weyer-Nichols,

Jeffrey I. Garcia-Sanchez

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(8), P. 887 - 887

Published: July 23, 2024

Macrophages are vital components of the immune system and serve as first line defense against pathogens. Macrophage colony-stimulating factor (M-CSF) induces macrophage differentiation from bone marrow-derived cells (BMDCs). Δ9-tetrahydrocannabiol (THC), a phytocannabinoid Cannabis plant, has profound anti-inflammatory properties with significant effects on myeloid cells. To investigate effect THC differentiation, we cultured BMDCs M-CSF in presence THC. Interestingly, markedly blocked into CD45 + CD11b F4/80+ macrophages. The was independent cannabinoid receptors CB1, CB2, well other potential such GPR18, GPR55, Adenosine 2A Receptor. RNA-seq analysis revealed that THC-treated displayed increase expression NRF2-ARE-related genes. KEGG pathway profiles correlated ferroptosis glutathione metabolism pathways. Fluorescence-based labile iron assays showed had significantly increased levels. Finally, THC-exposed decreased levels intracellular ROS. unique molecular property to block Fenton Reaction, thus preventing ROS is normally induced by high Together, these studies demonstrated blocks M-CSF-induced inhibiting production through both induction gene prevention formation via Reaction.

Language: Английский

Citations

1
Cadmium-induced Carcinogenesis in Respiratory Organs and the Prostate: Insights from Three Perspectives on Toxicogenomic Approach DOI Open Access
Jun Lee, Dong Yeop Shin, Yujin Jang

et al.

Journal of Cancer Prevention, Journal Year: 2023, Volume and Issue: 28(4), P. 150 - 159

Published: Dec. 30, 2023

Cadmium (Cd) exposure primarily occurs through inhalation, either by smoking or occupational to contaminated air.Upon Cd ultimately reaches the prostate bloodstream.In this review, we investigate carcinogenic potential of in both respiratory organs and prostate.Specifically, review examines cellular metabolism, comprehensive toxicity, mechanisms exploring gene ontology, biological networks, adverse outcome pathways.In organs, induces lung cancer altering expression IL1B FGF2, causing DNA damage, reducing cell junction integrity, promoting apoptosis.In prostate, modifying EDN1 HMOX1, leading abnormal protein activities maturation, suppressing tumor suppressors, inducing apoptosis.Collectively, provides a understanding two different adopting toxicogenomic approaches.These insights can serve as foundation for further research on cadmium-induced cancer, contributing establishment future prevention strategies.

Language: Английский

Citations

3
The Effect of Phytocannabinoids and Endocannabinoids on Nrf2 Activity in the Central Nervous System and Periphery DOI Creative Commons
Pietro Marini, Mauro Maccarrone, Luciano Saso

et al.

Neurology International, Journal Year: 2024, Volume and Issue: 16(4), P. 776 - 789

Published: July 18, 2024

The relationship between nuclear factor erythroid 2-related 2 (Nrf2) and phytocannabinoids/endocannabinoids (pCBs/eCBs) has been investigated in a variety of models peripheral illnesses, with little clarification on their interaction within the central nervous system (CNS). In this context, evidence suggests that Nrf2-pCBs/eCBS is relevant modulating peroxidation processes antioxidant system. Nrf2, one regulators cellular redox homeostasis, appears to have protective role toward damaging insults neurons glia by enhancing those genes involved regulation homeostatic processes. Specifically microglia macroglia cells, Nrf2 can be activated, its signaling pathway modulated, both pCBs eCBs. However, precise effects eCBs are not completely elucidated yet, making potential clinical employment still fully understood.

Language: Английский

Citations

0
Exploring the Therapeutic Potential of Cannabidiol in U87MG Cells: Effects on Autophagy and NRF2 Pathway DOI Creative Commons
Laura Giannotti, Benedetta Di Chiara Stanca, Francesco Spedicato

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 14(1), P. 18 - 18

Published: Dec. 26, 2024

Cannabinoids include both endogenous endocannabinoids and exogenous phytocannabinoids, such as cannabidiol (CBD), have potential therapeutic agents in cancer treatment due to their selective anticancer activities. CBD exhibits antioxidant pro-oxidant effects depending on its concentration cell types. These properties allow influence oxidative stress responses potentially enhance the efficacy of antitumor therapies. In this study, we treated U87MG glioma cells with low dose (1 μM) evaluated molecular effects. Our findings indicate that reduced viability by 20% (p < 0.05) through alteration mitochondrial membrane potential. The redox status caused an attempt rescue functionality nuclear localization GABP transcription factor involved mitochondria biogenesis. Moreover, increase autophagic flux, supported Beclin-1 ratio LC3-II/LC3-I. Due alteration, pro-apoptotic proteins were induced without activating apoptotic effectors Caspase-3 or Caspase-7. study NRF2 ubiquitin-binding protein p62 expression revealed levels CBD-treated cells. conclusion, low-dose makes more vulnerable cytotoxic effects, reducing dynamics while increasing flux systems. This explains mechanisms which respond treatment. highlight CBD, suggesting modulating autophagy pathways could represent a promising strategy for glioblastoma

Language: Английский

Citations

0