Investigation of juglone effects on metastasis and angiogenesis in pancreatic cancer cells

Avcı, Ebru; Arıkoğlu, Hilal; Kaya, Dudu Erkoç

doi:10.1016/j.gene.2016.05.001

Cited by 47 publications

(31 citation statements)

References 42 publications

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“…An increasing number of studies have reported that EMT serves a role in metastatic progression of PC and treatment resistance (16,17). Previous data have indicated that juglone may be a useful anti-proliferative and anti-invasive agent for certain types of cancer (10)(11)(12). In this study, it was demonstrated that juglone can modulate the migration and invasion of PC cells.…”

Section: Discussionmentioning

confidence: 60%

“…Akt activation leads to increased phosphorylation of the 9th residue of GSK3β, which facilitates GSK3β ubiquitination and prevents its participation in the degradation of Snail (8,9). Juglone (5-hydroxy-1, 4-naphthoquinone) is a natural compound that is isolated from plants and has been reported to possess potent cytotoxic properties in vitro against human leukemia, cervical carcinoma and pancreatic cancer cell lines (10)(11)(12). In an earlier study, the authors of the present study reported the effect of juglone on ovarian cancer cells and concluded that juglone likely induced apoptosis via the mitochondrial pathway and reduced cell invasiveness by decreasing matrix metalloproteinase expression (13).…”

Section: Introductionmentioning

confidence: 99%

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Juglone suppresses epithelial‑mesenchymal transition in prostate cancer cells via the protein kinase B/glycogen synthase kinase‑3β/Snail signaling pathway

Fang

Chen

et al. 2018

Oncol Lett

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Epithelial-mesenchymal transition (EMT) serves an important role in the metastasis of prostate cancer. Juglone is a natural compound isolated from plants that is reported to possess potent cytotoxic properties. However, there are no studies on the anti-EMT effect of juglone in prostate cancer, or its potential underlying mechanisms of action. In the present study, the effect of juglone on the EMT of prostate cancer cells was investigated. Transwell assays were used to demonstrate that juglone inhibits the migration and invasion of the prostate cancer (PC) LNCaP and LNCaP-AI cell lines. Results from western blot analysis demonstrated that juglone increases the expression of the epithelial marker E-cadherin while decreasing the expression of mesenchymal markers (N-cadherin and Vimentin) in a dose-dependent manner. The data from the present study also revealed that juglone downregulates the expression of Snail, a repressor of E-cadherin and an inducer of EMT. Furthermore, juglone prevented inactivation of glycogen synthase kinase-3β (GSK-3β), an endogenous inhibitor of Snail in a dose-dependent manner. Lithium chloride (LiCl), a GSK-3β inhibitor, prevented juglone-mediated downregulation of Snail expression and upregulation of E-cadherin. In addition, phosphorylation and subsequent activation of protein kinase B (Akt), which is known to phosphorylate GSK-3β at serine 9 (Ser9), leading to its inhibition, were significantly decreased by juglone in LNCaP and LNCaP-AI cells. Inhibition of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway by LY294002 augmented juglone-mediated GSK-3β activity by inhibiting Ser9 phosphorylation. These findings indicated that juglone suppresses EMT via the Akt/GSK-3β/Snail pathway, consequently decreasing the invasiveness of PC cells.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Juglone suppresses epithelial‑mesenchymal transition in prostate cancer cells via the protein kinase B/glycogen synthase kinase‑3β/Snail signaling pathway

Fang

Chen

et al. 2018

Oncol Lett

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“…Similarly, juglone, a lipid-soluble drug, has been widely used as a chemotherapeutic agent in Chinese herbal medicine against various tumors, including leukaemia [10], melanoma [11], gastric cancer [12] and pancreatic cancer [13] through the activation of apoptotic caspase cascade and the increase of ROS (reactive oxygen species) [14, 15]. Recently, juglone has been found to inhibit cell proliferation and to reduce the invasiveness of C6 rat glioma cells in vitro [16].…”

Section: Introductionmentioning

confidence: 99%

Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma

Zhang

et al. 2017

BMC Neurol

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BackgroundJuglone is a natural pigment, which has cytotoxic effect against various human tumor cells. However, its cytotoxicity to glioma cells, especially to tumor stem-like cells (TSCs) has not been demonstrated.MethodsTSCs of glioma were enriched from U87 and two primary cells (SHG62, and SHG66) using serum-free medium supplemented with growth factors, including bFGF, EGF and B27. After treatment of juglone with gradient concentrations (0, 10, 20, and 40 μM), the viability and apoptosis of TSCs were evaluated by WST-8 assay and flow cytometry. Reactive oxygen species (ROS) was labeled by the cell-permeable fluorescent probe and detected with flow cytometry. ROS scavenger (NAC) and p38-MAPK inhibitor (SB203580) were applied to resist the cytotoxic effect. Caspase 9 cleavage and p38 phosphorylation (P-p38) were quantified by western blot. Juglone as well as temozolomide (TMZ) were administrated in intracranial xenografts and MR scan was performed every week to evaluate the anti-tumor effect in vivo.ResultsJuglone could obviously inhibit the proliferation of TSCs in glioma by decreasing cell viability (P < 0.01) and inducing apoptosis (P < 0.01), which was accompanied by increased caspase 9 cleavage in a dose-dependent manner (P < 0.01). In the meantime, juglone could generate ROS significantly and increase p38 phosphorylation (P < 0.01). In addition, pretreatment with ROS scavenger or p38-MAPK inhibitor could reverse juglone-induced cytotoxicity (P < 0.01). More importantly, juglone could also suppress tumor growth in vivo and improve the survival of U87-bearing mice compared with control (P < 0.05), although TMZ seemed to have better effect.ConclusionsJuglone could inhibit the growth of TSCs in gliomas through the activation of ROS-p38-MAPK pathway in vitro, and the anti-glioma effect was validated in vivo, which offers a potential therapeutic agent to gliomas.

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“…At present, natural products are considered as potential therapeutic agents, for example: matrine could inhibit cell cycle, 20) camptothecin could block cells proliferation, 21) and podophyllotoxin could induce cells apoptosis. 22) Accordingly, juglone has been extensively applied as chemotherapeutic agent in Chinese herbal medicine for various tumors, such as leukaemia, 5) melanoma, 6) gastric cancer, 7) and pancreatic cancer 23) through activating caspase pathway and the increase of reactive oxygen species (ROS). 24) At present, it is found that juglone could prohibit cell proliferation and induce apoptosis of in-vitro HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

Juglone Inhibits Proliferation of HPV-Positive Cervical Cancer Cells Specifically

Zhao

Song

Zhao

et al. 2019

Biological & Pharmaceutical Bulletin

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Human papillomaviruses (HPVs), such as HPV 16 and HPV 18 are related to cervical cancer. Therefore, it is important to inhibit HPV-positive cervical cancer for treating cervical cancer. This study is aiming at investigating the proposed molecular mechanism, which underlies the antineoplastic potential of the aqueous extract of juglone of HPV-positive cervical cancer cells. According to the results, it is showed that, juglone prohibited HPV positive cervical cancer cells' growth through dose-dependent way. Nevertheless, when pin 1 was knocked down, the proliferation inhibition reduced. The detection of apoptosis and cell cycle also illustrated that juglone influenced HPV positive cells. Western blot expressed the influence mechanism that it affected the B-cell lymphoma 2 (Bcl-2) family and later activated the Caspase-depended apoptosis way. It is contributable for this study to understand the mechanism of inhibiting HPV positive cells by juglone and it also provides an effective strategy for the application of it in the future.

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Investigation of juglone effects on metastasis and angiogenesis in pancreatic cancer cells

Cited by 47 publications

References 42 publications

Juglone suppresses epithelial‑mesenchymal transition in prostate cancer cells via the protein kinase B/glycogen synthase kinase‑3β/Snail signaling pathway

Juglone suppresses epithelial‑mesenchymal transition in prostate cancer cells via the protein kinase B/glycogen synthase kinase‑3β/Snail signaling pathway

Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma

Juglone Inhibits Proliferation of HPV-Positive Cervical Cancer Cells Specifically

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