A Multi-targeted Natural Flavonoid Myricetin Suppresses Lamellipodia and Focal Adhesions Formation and Impedes Glioblastoma Cell Invasiveness and Abnormal Motility

Zhao, Hua; Wang, Gang; Wu, Chang Peng; Zhou, Xiu Ming; Wang, Jing; Chen, Zhong Ping; To, Shing Shun Tony; Li, Wei Ping

doi:10.2174/1871527317666180611090006

Cited by 20 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this review, we outlined the pharmacological effects of myricetin in the nervous system. Myricetin can produce preventive and therapeutic effects in nervous system disorders through anti-oxidation ( Wu et al, 2016 ), anti-proliferation ( Siegelin et al, 2009 ; Zhao et al, 2018 ; Li et al, 2021 ), and anti-neuroinflammation ( Jang et al, 2020 ; Boriero et al, 2021 ). The activation of the Nrf2 ( Wu et al, 2016 ), ERK1/2 ( Wang et al, 2017 ; Jang et al, 2020 ), Akt ( Sun et al, 2018 ), CREB ( Lei et al, 2012 ), and BDNF ( Sun et al, 2019 ), the inhibition of intracellular Ca 2+ increase and JNK-p38 activation ( Oyama et al, 1994 ; Hagenacker et al, 2010 ; Chang et al, 2015 ; Sun et al, 2018 ; Jang et al, 2020 ), and the suppression of mutant protein aggregation ( Joshi et al, 2019 ) and PVN neuronal activity ( Ma and Liu, 2012 ; Zhang et al, 2012 ) may also mediate the neuroprotective effects of myricetin in the nervous system.…”

Section: Discussionmentioning

confidence: 99%

“…Bcl-2 and the short isoform of c-FLIP, two proteins which can inhibit TRAIL-triggered cellular apoptosis, appear to mediate the sensitization effect of myricetin in glioblastoma cells, as their expression can be down-regulated by myricetin incubation (50 μM), and their overexpression can abrogate the facilitation effect of myricetin on TRAIL-induced apoptosis of glioblastoma cells ( Siegelin et al, 2009 ). In another study by Zhao et al (2018) , myricetin incubation (≥20 µM) was found to inhibit glioblastoma cell proliferation, migration, and invasion by blocking the formation of lamellipodia, focal adhesions, membrane ruffles, and vasculogenic mimicry in a manner dependent on the suppression of Akt, c-Jun, Rho-associated protein kinase 2 (ROCK2), paxillin, and cortactin phosphorylation. In U251 human glioma cells, myricetin incubation (5, 15, 30, 60, 120, 240 μM) was found to alter the glioma cell shape, which is likely associated with the promotion of cellular apoptosis ( Li et al, 2021 ).…”

Section: Pharmacological Effects Of Myricetin In Gliomamentioning

confidence: 97%

See 1 more Smart Citation

Pharmacological Actions of Myricetin in the Nervous System: A Comprehensive Review of Preclinical Studies in Animals and Cell Models

Xiang

Huang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Myricetin is a natural flavonoid extracted from a variety of plants, such as medicinal herbs, vegetables, berries, and tea leaves. A growing body of evidence has reported that myricetin supplementation display therapeutic activities in a lot of nervous system disorders, such as cerebral ischemia, Alzheimer’s disease, Parkinson’s disease, epilepsy, and glioblastoma. Myricetin supplementation can also protect against pathological changes and behavioral impairment induced by multiple sclerosis and chronic stress. On the basis of these pharmacological actions, myricetin could be developed as a potential drug for the prevention and/or treatment of nervous system disorders. Mechanistic studies have shown that inhibition of oxidative stress, cellular apoptosis, and neuroinflammatory response are common mechanisms for the neuroprotective actions of myricetin. Other mechanisms, including the activation of the nuclear factor E2-related factor 2 (Nrf2), extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (Akt), cyclic adenosine monophosphate-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) signaling, inhibition of intracellular Ca2+ increase, inhibition of c-Jun N-terminal kinase (JNK)-p38 activation, and suppression of mutant protein aggregation, may also mediate the neuroprotective effects of myricetin. Furthermore, myricetin treatment has been shown to promote the activation of the inhibitory neurons in the hypothalamic paraventricular nucleus, which subsequently produces anti-epilepsy effects. In this review, we make a comprehensive understanding about the pharmacological effects of myricetin in the nervous system, aiming to push the development of myricetin as a novel drug for the treatment of nervous system disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Pharmacological Effects Of Myricetin In Gliomamentioning

confidence: 97%

Pharmacological Actions of Myricetin in the Nervous System: A Comprehensive Review of Preclinical Studies in Animals and Cell Models

Xiang

Huang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…[ 168–170 ]. Myricetin, a flavonoid shows anti-migratory and antiinvasive properties against GBM cells [ 171 ]. The same compound reduces cytotoxic protein aggregates by modulating the protein degradation potential of 26S proteasome [ 168 ].…”

Section: Discussionmentioning

confidence: 99%

Amyloids and brain cancer: molecular linkages and crossovers

2023

View full text Add to dashboard Cite

Amyloids are high-order proteinaceous formations deposited in both intra- and extracellular spaces. These aggregates have tendencies to deregulate cellular physiology in multiple ways; for example, altered metabolism, mitochondrial dysfunctions, immune modulation etc. When amyloids are formed in brain tissues, the endpoint often is death of neurons. However, interesting but least understood is a close connection of amyloids with another set of conditions in which brain cells proliferate at an extraordinary rate and form tumor inside brain. Glioblastoma is one such condition. Increasing number of evidence indicate a possible link between amyloid formation and depositions in brain tumors. Several proteins associated with cell cycle regulation and apoptotic pathways themselves have shown to possess high tendencies to form amyloids. Tumor suppressor protein p53 is one prominent example that mutate, oligemerize and form amyloids leading to loss- or gain-of-functions and cause increased cell proliferations and malignancies. In this review article, we present available examples, genetic links and common pathways that indicate that possibly the two distantly placed pathways: amyloid formation and developing cancers in the brain have similarities and are mechanistically intertwined together.

show abstract

“…Myricetin (Fig. 1) is considered as a multi-targeted natural product with potential anti-migratory and antiinvasive effects based on in vitro cellular assays [37]. Recent preclinical studies showed that myricetin represses the malignant progression of prostate cancer [38].…”

Section: Myricetinmentioning

confidence: 99%

Cranberry anti-cancer compounds and their uptake and metabolism: An updated review

Prasain

Grubbs

Barnes

2020

JBR

View full text Add to dashboard Cite

Consumption of cranberry fruits or juice rich in polyphenols is associated with a wide range of potential health benefits. We and others have previously showed that cranberry juice concentrate and its phytochemicals, flavonols, anthocyanins and A-type proanthocyandins, may have potential to be chemopreventive agents. Although a number of cranberry constituents have been implicated in cancer prevention, our understanding about which metabolites are bio-available to reach target sites and thereby elicit cancer chemopreventive properties is still lacking. However, poor plasma bioavailability of cranberry constituents may be overcome by their potential interactions with gut microbiota by providing cancer prevention through induction of compositional and functional modifications of gut microbiota. Well-designed clinical trials evaluating metabolic and gut microbiome changes associated with cranberry consumption would provide useful information about the cancer patient's response to dietary intervention with cranberry constituents.

show abstract

A Multi-targeted Natural Flavonoid Myricetin Suppresses Lamellipodia and Focal Adhesions Formation and Impedes Glioblastoma Cell Invasiveness and Abnormal Motility

Abstract: In conclusion, myricetin is a multi-targeted drug that has potent anti-migratory and antiinvasive effects on GBM cells, and suppresses formation of lamellipodia and focal adhesions, suggesting that it may serve as an alternative option for GBM treatment.

Cited by 20 publications

References 0 publications

Pharmacological Actions of Myricetin in the Nervous System: A Comprehensive Review of Preclinical Studies in Animals and Cell Models

Pharmacological Actions of Myricetin in the Nervous System: A Comprehensive Review of Preclinical Studies in Animals and Cell Models

Amyloids and brain cancer: molecular linkages and crossovers

Cranberry anti-cancer compounds and their uptake and metabolism: An updated review

Contact Info

Product

Resources

About