Curcumin and Solid Lipid Curcumin Particles Induce Autophagy, but Inhibit Mitophagy and the PI3K-Akt/mTOR Pathway in Cultured Glioblastoma Cells

Maiti, Panchanan; Scott, Jason; Sengupta, Dipanwita; Gharaibeh, Abeer; Dunbar, Gary

doi:10.3390/ijms20020399

Cited by 85 publications

(64 citation statements)

References 60 publications

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“…Moreover, curcumin treatment in A172 human glioblastoma cells leads to cell death by inducing autophagy flux [84]. Another study confirmed that curcumin promotes autophagy in glioblastoma cells while it inhibits mitophagy [85]. Curcumin also blocks invasion and migration potential of glioblastoma U87 cells by decreasing the expression of fascin, an actin-binding protein involved in migration and invasion [86].…”

Section: Curcumin Effects On Central Nervous System Cancersmentioning

confidence: 91%

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

Perrone

Sampaolo

Melone

2020

Cancers

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Efficacious therapies are not available for the cure of both gliomas and glioneuronal tumors, which represent the most numerous and heterogeneous primary cancers of the central nervous system (CNS), and for neoplasms of the peripheral nervous system (PNS), which can be divided into benign tumors, mainly represented by schwannomas and neurofibromas, and malignant tumors of the peripheral nerve sheath (MPNST). Increased cellular oxidative stress and other metabolic aspects have been reported as potential etiologies in the nervous system tumors. Thus polyphenols have been tested as effective natural compounds likely useful for the prevention and therapy of this group of neoplasms, because of their antioxidant and anti-inflammatory activity. However, polyphenols show poor intestinal absorption due to individual intestinal microbiota content, poor bioavailability, and difficulty in passing the blood–brain barrier (BBB). Recently, polymeric nanoparticle-based polyphenol delivery improved their gastrointestinal absorption, their bioavailability, and entry into defined target organs. Herein, we summarize recent findings about the primary polyphenols employed for nervous system tumor prevention and treatment. We describe the limitations of their application in clinical practice and the new strategies aimed at enhancing their bioavailability and targeted delivery.

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Section: Curcumin Effects On Central Nervous System Cancersmentioning

confidence: 91%

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

Perrone

Sampaolo

Melone

2020

Cancers

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“…In addition, cell survival markers were downregulated and cell death markers were upregulated by curcumin. All these effects were amplified in SLCP-treated cells in comparison to curcumin-treated cells [50].…”

Section: Cancermentioning

confidence: 93%

Effects of Plant and Animal Natural Products on Mitophagy

Shakeri

Bianconi

Pirro

et al. 2020

Oxidative Medicine and Cellular Longevity

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Mitophagy is a protected cellular process that is essential for autophagic removal of damaged mitochondria and for preservation of a healthy mitochondrial population. In the last years, a particular interest has been devoted in studying the effects of natural compounds on mitophagy. Different natural compounds may modulate mitochondrial oxidative phosphorylation, the production of mitochondrial reactive oxygen species, the expression of mitophagy-and autophagy-related genes, and the activities of transcription factors which regulate the expression of mitochondrial proteins, thereby controlling mitochondrial damage and mitophagy. Remarkably, since mitochondrial function has a crucial role in the pathogenesis of various diseases (e.g., cancer, atherosclerosis, Duchenne muscular dystrophy, diabetes complications, Alzheimer's disease, and hepatic steatosis), these effects might have important therapeutic implications. In this review, preclinical studies investigating the role of different natural compounds in the modulation of mitophagy will be discussed.

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“…To compare the anti-amyloid potency, such as inhibition of Aβ42 aggregation after treatment with SLCP and natural Cur, the dot blot assay was performed, as described previously [50,51]. Brie y, Aβ42 peptide was dissolved in hexa uoro isopropanol (HFIP), mixed for 1 min and allowed to solubilize for 30 min at room temperature, and then the HFIP was evaporated under laminar hood to make a thin lm of peptide layer.…”

Section: Dot Blot Assaymentioning

confidence: 99%

“…buffer and a protease inhibitor cocktail (Sigma, Catalog no: P8340-5ML), as described previously [18,47,51]. The tissue homogenate was centrifuged at 13,300 rpm for 20 min at 4 o C, and the supernatant was collected, aliquoted with 20 µL in each PCR-tube and stored at -80 o C until needed.…”

Section: 2mentioning

confidence: 99%

Preservation of dendritic spine morphology and postsynaptic signaling markers after treatment with solid lipid curcumin particles in the 5xFAD mouse model of Alzheimer’s disease

Maiti¹,

Dunbar²

2020

Preprint

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Background Synaptic failure is one of the principal events associated with cognitive dysfunction in Alzheimer’s disease (AD). Preservation of existing synapses and prevention of synaptic loss are promising strategies to preserve cognitive function in AD patients. As a potent natural anti-oxidant, anti-amyloid, anti-inflammatory polyphenol, curcumin (Cur) shows great promise as a therapy for AD. However, hydrophobicity of natural Cur limits its solubility, stability, bioavailability and clinical utility for AD therapy. We have demonstrated that solid lipid curcumin particles (SLCP) have greater therapeutic potential than natural Cur in vitro and in vivo models of AD. In the present study, we have investigated whether SLCP has any preservative role on affected dendritic spines and synaptic markers in 5xFAD mice.Methods Six- and 12-month-old 5xFAD and age-matched wild-type mice received oral administration of SLCP (100 mg/kg body weight) or equivalent amounts of vehicle for 2 months. Neuronal morphology, neurodegeneration and amyloid plaque load were investigated from prefrontal cortex (PFC), entorhinal cortex (EC), CA1, CA3 and the subicular complex (SC). Further, dendritic spine density of apical and basal branches were studied by Golgi-Cox stain. Further, synaptic markers, such as synaptophysin, PSD95, Shank, Homer, Drebrin, kalirin-7, CREB and phosphorylated CREB (pCREB) were studied using Western blots. Finally, cognitive and motor functions were assessed using open field, novel object recognition (NOR) and Morris water maze (MWM) tasks after treatment with SLCP.Results We observed an increase number of pyknotic and degenerated cells in all these brain areas in 5xFAD mice and SLCP treatment partially protected against those losses. Decrease in dendritic arborization and dendritic spine density from primary and secondary apical and basal branches were observed in PFC, EC, CA1, CA3 in both 6- and 12-month-old 5xFAD mice and SLCP treatments partially preserved the normal morphology of these dendritic spines. In addition, pre- and post-synaptic protein markers were also restored by SLCP treatment. Furthermore, SLCP treatment improved NOR and cognitive function in 5xFAD mice.Conclusions Overall, these findings indicate that use of SLCP exerts neuroprotective properties by decreasing amyloid plaque burden, preventing neuronal death, as well as preservation of dendritic spine density and synaptic markers in the 5xFAD mice.

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Curcumin and Solid Lipid Curcumin Particles Induce Autophagy, but Inhibit Mitophagy and the PI3K-Akt/mTOR Pathway in Cultured Glioblastoma Cells

Cited by 85 publications

References 60 publications

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

Effects of Plant and Animal Natural Products on Mitophagy

Preservation of dendritic spine morphology and postsynaptic signaling markers after treatment with solid lipid curcumin particles in the 5xFAD mouse model of Alzheimer’s disease

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