Molecular mechanism of anti-cancerous potential of Morin extracted from mulberry in Hela cells

Zhang, Qi; Zhang, Fang; Thakur, Kiran; Wang, Jun; Wang, Hao; Hu, Fei; Zhang, Jianguo; Wei, Zhao‐Jun

doi:10.1016/j.fct.2017.07.002

Cited by 76 publications

(33 citation statements)

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“…This observation was associated with a decrease in the number of cells in the G0/G1 phase. A similar effect on the HeLa cancer cell cycle arrest at the G2/M phase after morin treatment observed Zhang et al [19].…”

Section: Discussionsupporting

confidence: 80%

“…All hydroxyl groups are responsible for the free radical-scavenging properties of flavonoids [18]. Morin has a promising anti-cancerous activity by reducing DNA damage and modulating signaling pathways responsible for proliferation and differentiation, which could lead to cell-cycle arrest and apoptosis [19,20]. Morin downregulated NF-κB which inhibited the inflammatory gene cascade along with the downregulation of several factors such as an inhibitor of apoptosis protein 1 and 2, in cell proliferation, cyclooxygenase-2 and cyclin D1, and invasion such as matrix metalloproteinases [21].…”

Section: Epigenetic Modulation Of Emt: Natural Compounds As An Alternmentioning

confidence: 99%

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Morin exerts anti-metastatic, anti-proliferative and anti-adhesive effect in ovarian cancer cells: an in vitro studies

2020

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The influence of morin hydrate on changes of proliferative, metastatic, and adhesive potential of human ovarian cancer cells concerning the influence of decitabine, and decitabine with trichostatin A, and in comparison to untreated cells, were analyzed. The effect of morin hydrate, decitabine, and trichostatin A were examined in A2780 and SKOV-3 ovarian cancer cell lines using MTS assay, clonogenic assay, adhesion to endothelial HMEC-1 cells, transwell migration assay and cell cycle analysis. The expression level of epithelial to mesenchymal transition (EMT) markers was quantified using PCR Array in relation to the level of global methylation determined with Methylated DNA Quantification Kit. We observed statistically significant inhibition of adhesive and migratory potential of both cell lines and the accumulation of G0/G1 phase A2780 cells after treatment with morin hydrate. Our studies confirmed the influence of morin hydrate on down-regulation of genes considered as up-regulated during EMT, and up-regulation of some genes considered as down-regulated during EMT in A2780 and SKOV-3 cells. Phenotypic changes were associated with molecular changes in cells, eg. decrease of the expression level of genes associated with adhesion, and an increase of genes down-regulated during EMT, after morin hydrate treatment in comparison to untreated control cells in both cell lines, were observed. Keywords Adhesion • Epithelial to mesenchymal transition • Metastasis • Morin hydrate • Ovarian cancer cells Abbreviations ATCC American type culture collection DNMT DNA methyltransferase ECACC European collection of authenticated cell cultures ECM Extracellular matrix EMT Epithelial to mesenchymal transition EOC Epithelial ovarian cancer HAT Histone acetyltransferase HDAC Histone deacetylase MET Mesenchymal to epithelial transition SAM S-sdenosyl-l-methionine TSA Trichostatin A

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Section: Discussionsupporting

confidence: 80%

Section: Epigenetic Modulation Of Emt: Natural Compounds As An Alternmentioning

confidence: 99%

Morin exerts anti-metastatic, anti-proliferative and anti-adhesive effect in ovarian cancer cells: an in vitro studies

2020

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“…Thus, modulating activity of cell cycle regulators may be a good strategy for inhibiting PDGFmediated VSMC proliferation. Although morin displays anti-proliferative activity against both normal hepatocytes (MadanKumar et al 2014) and cancerous cells (Shin et al 2017;Zhang et al 2018), little has been reported on the cell cycle distribution profile mediated by morin in VSMCs. Therefore, we investigated cell cycle phase distribution using flow cytometry with morin-treated VSMCs.…”

Section: Discussionmentioning

confidence: 99%

Morin inhibits PDGF-induced proliferation, migration, and invasion of vascular smooth muscle cells via modulating p27KIP1, AKT, and MMP-9 activities

Shin

Ko²,

Noh³

et al. 2018

gpb

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Hyper-proliferation and migration of vascular smooth muscle cells (VSMCs) are closely associated with atherosclerosis. Recently, the flavonol morin has been reported to exhibit potent anti-oxidant and anti-inflammatory activities. Therefore, we investigated molecular mechanisms of morin in VSMCs stimulated by PDGF. Morin effectively inhibited PDGF-stimulated proliferation of VSMCs through a G1 cell-cycle arrest, leading to down-regulation of CDK2, CDK4, cyclin D1, and cyclin E proteins. Interestingly, PDGF markedly down-regulated p27KIP1 protein expression; however, morin treatment restored the p27KIP1expression to the basal level. Morin did not affect phosphorylation of MAPKs (ERK, p38, and JNK); however, phosphorylation of AKT was dramatically suppressed by morin in PDGF-stimulated VSMCs. Using the PI3K inhibitor, LY294002, we revealed that AKT is a key regulator in the inhibitory mechanism of morin against PDGF-induced proliferation of VSMCs. Morin disturbed migratory and invasive potential of VSMCs via suppression of matrix metalloproteinase-9 (MMP-9) activity. Using electrophoretic mobility shift assays, we verified that NF-κB, AP-1, and Sp-1 transcription factors are implicated in the mode of action of morin, which suppresses the MMP-9 activity in PDGF-induced VSMCs. Based on the results, we believe that morin may be a potential therapeutic agent for atherosclerosis without negative side effect.

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“…Morin is a neuroactive polyphenolic compound obtained from mulberry leaves (Kapoor & Kakkar, ). Previous preclinical investigations have reported that morin demonstrated immunomodulatory and antineuroinflammatory (Jung et al, ; Ola et al, ), antioxidant (Ola et al, ), antidiabetic (Ola et al, ), antixanthine (Yu, Fong, & Cheng, ), antihypertensive (Prahalathan, Saravanakumar, & Raja, ), and anticancer (Zhang et al, ) properties. Recent studies have also shown that morin produces antidepressant (Ben‐Azu et al, ), antipsychotic (Ben‐Azu, Aderibigbe, Omogbiya, Ajayi, & Iwalewa, ; Ben‐Azu et al, ; Ben‐Azu, Aderibigbe, Eneni, et al, ; Ben‐Azu et al, ), anxiolytic (Mangaiarkkarasi, Viswanathan, Ramaswamy, & Tharani, ), antiamnesic (Lemkul & Bevan, ), and anti‐Parkinsonia (Zhang et al, ) properties in behavioral paradigms.…”

Section: Introductionmentioning

confidence: 99%

Involvement of l‐arginine‐nitric oxide pathway in the antidepressant and memory promoting effects of morin in mice

Ben‐Azu

Aderibigbe

Ajayi

et al. 2019

Drug Development Research

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l‐Arginine‐nitric oxide pathway has been reported to be involved in the mediation of the psychopharmacological effects of many psychotropic drugs. Previous studies have shown that morin, a psychotropic compound isolated from mulberry leaf produces functional psychopharmacological effects indicative of antidepressant, antipsychotic, anxiolytic and nootropic properties. However, the role of l‐arginine‐nitric oxide pathway in the psychotropic effects of morin has not been fully investigated, hence, the need for this study. Male Swiss mice were pretreated individually or in combination with nitric oxide precursor [l‐arginine (750 mg/kg, i.p.)], competitive nonselective nitric oxide synthase (NOS) inhibitor [N(G)‐nitro‐l‐arginine methyl ester (l‐NAME, i.p) (50 mg/kg)] or selective neuronal NOS inhibitor [methylene blue (3.75 mg/kg, i.p)] prior to morin (100 mg/kg, i.p.) or saline (10 mL/kg, i.p.) treatment. Psychopharmacological activities were then evaluated 30 min later using open field, Y‐maze, and forced swim tests. l‐Arginine significantly reversed the effects of morin on locomotion, memory and depression in mice. The reduced motor activity and enhanced memory function produced by morin were significantly attenuated by methylene blue but augmented the antimobility activity of morin in the FST. Moreover, l‐NAME potentiated the psychopharmacological effects of morin in the open field and forced swim tests but reduced its memory promoting effect. Meanwhile, morin supplementation reversed the effects of l‐arginine on l‐NAME‐treated mice in all behavioral models. The results of this study suggest that l‐arginine‐nitric oxide pathway might play a role in the modulation of the antidepressant and memory promoting effects of morin in mice.

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Molecular mechanism of anti-cancerous potential of Morin extracted from mulberry in Hela cells

Cited by 76 publications

References 50 publications

Morin exerts anti-metastatic, anti-proliferative and anti-adhesive effect in ovarian cancer cells: an in vitro studies

Morin exerts anti-metastatic, anti-proliferative and anti-adhesive effect in ovarian cancer cells: an in vitro studies

Morin inhibits PDGF-induced proliferation, migration, and invasion of vascular smooth muscle cells via modulating p27KIP1, AKT, and MMP-9 activities

Involvement of l‐arginine‐nitric oxide pathway in the antidepressant and memory promoting effects of morin in mice

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