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

Nowak, Ewa; Sypniewski, Daniel; Bednarek, Ilona

doi:10.1007/s11033-020-05293-x

Cited by 21 publications

(16 citation statements)

References 37 publications

(49 reference statements)

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“…Naringenin has been shown to control cell differentiation and proliferation by acting as an anti-mitogen. It has been shown that mTOR signaling suppression effectively postpones the development of endometrial, breast, and ovarian cancers (Martínez-Rodríguez et al, 2020;Nowak et al, 2020;Treeck et al, 2006). Morin also improved ACR-induced hepatotoxicity and nephrotoxicity by modulating the protein levels of mTOR signalling pathways .…”

Section: Discussionmentioning

confidence: 99%

“…The remarkable suppression of adhesion and migration of SKOV-3 and A2780 cell lines together with the distinct regulation of autophagy and significant apoptotic induction was noticed after treatment with morin, although the exact autophagic mechanism of morin is still unknown (Nowak et al, 2020;Pal Singh et al, 2020). Autophagy activation has been implicated in cisplatin resistance, while autophagy suppression improves the effectiveness of morin in SKOV-3 cells (Bieg et al, 2018;Pal Singh et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

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Naringenin and morin reduces insulin resistance and endometrial hyperplasia in the rat model of polycystic ovarian syndrome through enhancement of inflammation and autophagic apoptosis

Yang

Liu

2022

Acta Biochim Pol

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Polycystic Ovary Syndrome (PCOS) is a gynecologic disorder with unsatisfactory treatment options. Hyperandrogenism and insulin resistance (IR) are two symptoms of PCOS. The majority of PCOS patients (approximately 50% to 70%) have IR and moderate diffuse inflammation of varying degrees. We investigated in-vitro and in-vivo effects of naringenin, morin and their combination on PCOS induced endometrial hyperplasia by interfering with the mTORC1 and mTORC2 signaling pathways. The vaginal smear test ensured the regular oestrous cycles in female rats. Serum cytokines (TNF-α & IL-6) were assessed using the ELISA test, followed by in-vivo and in-vitro determination of prominent gene expressions (mTORC1& C2, p62, LC3-II, and Caspase-3 involved in the inflammatory signaling mechanisms through RT-PCR, western bloting, or immunohistochemical analysis. In addition, the viability of naringenin or morin treated cells was determined using flow cytometry analysis. The abnormal oestrous cycle and vaginal keratosis indicated that PCOS was induced successfully. The recovery rate of the oestrous cycle with treatments was increased significantly (P<0.01) when compared to the PCOS model. Narigenin, morin, or a combination of the two drugs substantially decreased serum insulin, TNF-α, IL-6 levels with improved total anti-oxidant capacity and SOD levels (P<0.01). Treatments showed suppression of HEC-1-A cells proliferation with increased apoptosis (P<0.01) by the upregulation of Caspase-3 expression, followed by downregulation of mTORC, mTORC1, and p62 (P<0.01) expressions with improved LC3-II expressions (P<0.05) respectively. The histological findings showed a substantial increase in the thickness of granulose layers with improved corpora lutea and declined the number of cysts. Our findings noticed improved inflammatory and oxidative microenvironment of ovarian tissues in PCOS treated rats involving the autophagic and apoptotic mechanisms demonstrating synergistic in-vitro and in-vivo therapeutic effects of treatments on PCOS-induced endometrial hyperplasia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Naringenin and morin reduces insulin resistance and endometrial hyperplasia in the rat model of polycystic ovarian syndrome through enhancement of inflammation and autophagic apoptosis

Yang

Liu

2022

Acta Biochim Pol

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“…Human neuroblastoma SH-SY5Y cells -Reduced the BACE1 at mRNA and protein levels -Decreased the acetylated H3 in the BACE1 promoter regions through the upregulation of endogenous HDAC1-mediated deacetylation, which is independent of DNA methylation status ⇒ Galangin proposes a neuroprotective mechanism of polyphenols against alzheimer's disease through an epigenic modifications of AD-related genes ⇒ Kaempferol activates the IRE1-JNK-CHOP signaling from cytosol to nucleus, and G9a inhibition activates autophagic cell death in GC cells Inhibited the adhesive and migratory potential of both cell lines and the accumulation of G0/G1 phase A2780 cells -Induced the downregulation of genes considered as upregulated during EMT (epithelial to mesenchymal transition), and upregulation of some genes considered as downregulated during EMT in A2780 and SKOV-3 cells -Decreased the expression level of genes associated with adhesion -Increased genes downregulated during EMT ⇒ Morin induced a phenotypic changes due to some molecular changes in cells, eg., decrease in the expression level of genes associated with adhesion, and an increase in genes downregulated during EMT [212] Table 1. Cont.…”

Section: Galangin (Purchased)mentioning

confidence: 99%

“…Nowak et al [212] studied the effect of morine hydrate on alterations in proliferative, metastatic, and adherent capacity of human ovarian cancer cells (A2780 and SKOV-3) in the presence of decitabine, decitabine with trichostatin A. After treating all cell lines with morin hydrate, the authors observed a statistically significant reduction in adhesive and migratory capacity, as well as an accumulation of G 0 /G 1 phase.…”

Section: Morinmentioning

confidence: 99%

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions

et al. 2022

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Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers.

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“…In addition, its positional isomer morin, possesses comparable biological properties. Many reports highlighted the anticancer potential of this naturally occurring bioactive phytochemical [14,15]. Giving a glance to flavanones, pinocembrin showed several biological activities including anticancer, anti-inflammatory, antimicrobial, and antioxidant properties [16,17].…”

Section: Introductionmentioning

confidence: 99%

New Oleoyl Hybrids of Natural Antioxidants: Synthesis and In Vitro Evaluation as Inducers of Apoptosis in Colorectal Cancer Cells

et al. 2020

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Nowadays, the beneficial role of a healthy lifestyle, particularly emphasizing the quality of foods and cancer management, is accepted worldwide. Polyphenols and oleic acid play a key role in this context, but are still scarcely used as anti-cancer agents due to their bio-accessibility limits. Therefore, we aimed to synthesize a set of new oleoyl-hybrids of quercetin, morin, pinocembrin, and catechin to overcome the low bioavailability of polyphenols, throughout a bio-catalytic approach using pancreatic porcine lipase as a catalyst. The in vitro assays, using a wide panel of human cancer cell lines showed, mainly for two novel regioisomer oleoyl-hybrids of quercetin, a remarkable increase in apoptotic cell populations. We suggested that the DNA damage shown as ɣH2AX signals might be the major cause of apoptotic cell death. Finally, we demonstrated convincing data about two novel polyphenol-based hybrids displaying a highly selective anti-cancer cytotoxicity and being superior compared to their reference/parental compounds.

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

Cited by 21 publications

References 37 publications

Naringenin and morin reduces insulin resistance and endometrial hyperplasia in the rat model of polycystic ovarian syndrome through enhancement of inflammation and autophagic apoptosis

Naringenin and morin reduces insulin resistance and endometrial hyperplasia in the rat model of polycystic ovarian syndrome through enhancement of inflammation and autophagic apoptosis

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions

New Oleoyl Hybrids of Natural Antioxidants: Synthesis and In Vitro Evaluation as Inducers of Apoptosis in Colorectal Cancer Cells

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