Neferine inhibits epidermal growth factor-induced proliferation and migration of retinal pigment epithelial cells through downregulating p38 MAPK and PI3K/AKT signalling

Özal, Sadık Altan; Gürlü, Vuslat; Turkekul, Kader; Güçlü, Hande; Erdoğan, Suat

doi:10.1080/15569527.2020.1730882

Cited by 19 publications

(9 citation statements)

References 42 publications

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“… 42 Some researchers also cultured fibroblasts from the skin of patients with systemic sclerosis (SSC) and healthy patients, and PCR examination indicated that survivin mRNA expression in fibroblasts of patients with SSC was significantly increased, 43 suggesting that survivin may play a certain role during cell fibrosis. Some researchers have found the expression of survivin in ocular fibroblast diseases, such as proliferative vitreoretinopathy 44 and pterygium. 45 , 46 Following these studies, it is indicated that survivin may be involved in the scar formation process after glaucoma filtering surgery.…”

Section: Discussionmentioning

confidence: 99%

The Role of Survivin and Transcription Factor FOXP1 in Scarring After Glaucoma Surgery

Wang

Huang

Zeng

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose This study aims to elucidate the role and mechanism of survivin and FOXP1 in scarring after glaucoma surgery and to evaluate the prevention and treatment of excessive wound healing and scar formation in an in vitro model of glaucoma filtration surgery. Methods Human Tenon's capsule fibroblasts (HTFs) were used with TGF-β to establish an in vitro cell model after glaucoma, observe survivin expression in the cell model, and observe HTFs proliferation after treatment with survivin inhibitor YM155 and the expression of α-SMA and collagen type I. In addition, the effects of survivin and cell proliferation in HTFs after knockdown of FOXP1 were observed by Western blot analysis. Results Survivin was upregulated in HTFs after glaucoma surgery, and it could promote the cell proliferation of HTFs. After treatment with its inhibitor YM155, the cell proliferation of HTFs was inhibited, and the expression of α-SMA and collagen type I were decreased. The results showed that in knockdown of FOXP1, the expression of survivin was downregulated, and the cell proliferation of HTFs was significantly reduced. Conclusions This study demonstrates that targeting survivin with an inhibitory YM155 reduced fibrosis and the extracellular matrix (ECM), and it was regulated by the FOXP1 transcription factor. These results suggest that survivin could be a potential target for treating scar formation after glaucoma surgery. Translational Relevance Together with the results from previous survivin and FOXP1 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for antiscarring of glaucoma surgery.

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Section: Discussionmentioning

confidence: 99%

The Role of Survivin and Transcription Factor FOXP1 in Scarring After Glaucoma Surgery

Wang

Huang

Zeng

et al. 2022

Trans. Vis. Sci. Tech.

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“…These factors bind to and stimulate the autophosphorylation of transmembrane receptors on Tyr, subsequently participating in RPE cell EMT via PI3K/Akt pathway, ERK MAPK pathway, p38 MAPK pathway ( Fig. 3 ) ( Chen et al, 2016a ; Ozal et al, 2020 ). Chen et al (2012) explored the role of Wnt/β-catenin signaling in PVR, and found that when EGTA disrupted contact inhibition in RPE cells, EGF+FGF2 could activate Wnt signaling and increase nuclear levels of β-catenin, which interacts with TCF and/or LEF, leading to cell proliferation ( Fig.…”

Section: Survey Methodologymentioning

confidence: 99%

Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

Zou

Shan

et al. 2020

PeerJ

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Under physiological conditions, retinal pigment epithelium (RPE) is a cellular monolayer composed of mitotically quiescent cells. Tight junctions and adherens junctions maintain the polarity of RPE cells, and are required for cellular functions. In proliferative vitreoretinopathy (PVR), upon retinal tear, RPE cells lose cell-cell contact, undergo epithelial-mesenchymal transition (EMT), and ultimately transform into myofibroblasts, leading to the formation of fibrocellular membranes on both surfaces of the detached retina and on the posterior hyaloids, which causes tractional retinal detachment. In PVR, RPE cells are crucial contributors, and multiple signaling pathways, including the SMAD-dependent pathway, Rho pathway, MAPK pathways, Jagged/Notch pathway, and the Wnt/β-catenin pathway are activated. These pathways mediate the EMT of RPE cells, which play a key role in the pathogenesis of PVR. This review summarizes the current body of knowledge on the polarized phenotype of RPE, the role of cell-cell contact, and the molecular mechanisms underlying the RPE EMT in PVR, emphasizing key insights into potential approaches to prevent PVR.

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“…For example, in a 48 hr application, 10 µM neferine kills approximately 50% of ovarian cancer cells (Xu et al., 2016) and human osteosarcoma cells (Zhang et al., 2012); the same dose kills more than 80% of GIST cells (Xue et al., 2019). Moreover, the same concentration of neferine does not show antiproliferative effect in normal cells such as hepatocytes (Deng et al., 2017) and retina pigment epithelial cells (Ozal, Gurlu, Turkekul, Guclu, & Erdogan, 2020). According to study by Liang, Sun, and Liu (2019), human glioma cells show much more sensitivity to neferine.…”

Section: Discusionmentioning

confidence: 99%

Neferine inhibits proliferation and migration of human prostate cancer stem cells through p38 MAPK/JNK activation

Erdoğan

Turkekul

2020

J Food Biochem

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Cancer stem cells (CSCs) are one of the significant causes of cancer treatment failure and metastasis, as they have significant chemo‐and radio‐resistance leading to tumor recurrence. Here we investigated the possible anticancer properties of neferine, a natural alkaloid, on human prostate cancer (PCa) cells and their stem cells. CD44+ CSCs were isolated from androgen‐insensitive PC3 cells by magnetic‐activated cell sorting system (MACS). Neferine dose‐and time‐dependently inhibited the viability of PC3 and CSCs as well as androgen‐sensitive LNCaP cells through inducing apoptosis and cell cycle arrest at G1 phase. Neferine was shown to downregulate the expression of Bcl‐2 and CDK4, and upregulate caspase 3, clePARP, p21, p27, and p53. The treatment significantly inhibits the migration of CSCs. Neferine induces JNK and p38 MAPK phosphorylation, and downregulates PI3K and NF‐ĸβ signaling. In conclusion, neferine may have a therapeutic effect inhibiting the PCa cell proliferation as well as by eliminating CSCs. Practical applications Neferine is an alkaloid found in the seed embryo of Nelumbo nucifera and has recently been shown to have anticancer effects on various human cancer cells. More than 90% of cancer‐related deaths develop after metastasis, and CSCs are considered to be largely responsible for the cell migration and invasion. It has been shown that treatment of neferine kills not only PCa cells but also CSCs, and may contribute to the prevention of progression of PCa and metastasis by inhibiting cell proliferation and migration.

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Neferine inhibits epidermal growth factor-induced proliferation and migration of retinal pigment epithelial cells through downregulating p38 MAPK and PI3K/AKT signalling

Cited by 19 publications

References 42 publications

The Role of Survivin and Transcription Factor FOXP1 in Scarring After Glaucoma Surgery

The Role of Survivin and Transcription Factor FOXP1 in Scarring After Glaucoma Surgery

Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

Neferine inhibits proliferation and migration of human prostate cancer stem cells through p38 MAPK/JNK activation

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