Fructose-1,6-bisphosphate decreases IL-8 levels and increases the activity of pro-apoptotic proteins in HepG2 cells

Krause, Gabriele Catyana; Lima, Kelly Goulart; Haute, Gabriela Viegas; Schuster, Aline Daniele; Dias, Henrique Bregolin; Mesquita, Fernanda Cristina de; Pedrazza, Leonardo; Marczak, Elisa Simon; Basso, Bruno Souza; Velasque, Anderson Catarina; Martha, Bianca Andrade; Nunes, Fernanda Bordignon; Donadio, Márcio Vinı́cius Fagundes; Oliveira, Jarbas Rodrigues de

doi:10.1016/j.biopha.2017.01.178

Cited by 11 publications

(9 citation statements)

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“…In addition, activation of IL-8 signal transduction provided tumor cells with chemotherapeutic resistance [28, 29]. IL-8 activates several intracellular signaling pathways in downstream of G-protein-coupled receptor (GPCR) such as CXCR1 and CXCR2 on two kinds of cell surface.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Genistein inhibits stemness of SKOV3 cells induced by macrophages co-cultured with ovarian cancer stem-like cells through IL-8/STAT3 axis

Ning

Feng

Cao

et al. 2019

J Exp Clin Cancer Res

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BackgroundRecent studies showed that macrophages co-cultured with ovarian cancer stem-like cells (OCSLCs) induced SKOV3 cell stemness via IL-8/STAT3 signaling. Genistein (GEN) demonstrates chemopreventive activity in inflammation-associated cancers. The present study aimed to examine whether and if GEN inhibits the stemness of SKOV3 and OVCA-3R cells induced by co-culture of THP-1 macrophages and SKOV3-derived OCSLCs.MethodsThe co-culture was treated with or without different concentrations (10, 20, and 40 μmol/L) of GEN for 24 h. Depletion or addition of IL-8 in Co-CM and knockdown or overexpression of STAT3 in THP-1 macrophages was performed to demonstrate the possible associated mechanisms. The combined effects of GEN and STAT3 knockdown were examined with the nude mouse modle by co-injection of SKOV3-derived OCSLCs with THP-1 macrophages.ResultsOur results showed that GEN down-regulated CD163 and p-STAT3 expression of THP-1 macrophage, decreased the levels of IL-10, increased the levels of IL-12 and nitric oxide (NO) in the conditioned medium, and reduced the clonogenic and sphere-forming capacities and the expression of CD133 and CD44 in SKOV3 cells induced by co-culture of THP-1 macrophages and OCSLCs in a dose-dependent manner. Moreover, depletion or addition of IL-8 enhanced or attenuated the effect of GEN. Additionally, knockdown or overepression of STAT3 in THP-1 macrophages potentiated or attenuated the inhibitory effects of GEN. Importantly, STAT3 overexpression retrieved the effects of IL-8 combined with GEN depletion on M2 polarization of THP-1 macrophages and stemness of SKOV3 cells induced by co-culture. The combination of GEN and STAT3 knockdown cooperatively inhibited the growth of tumors co-inoculated with OCSLCs/THP-1 macrophages in nude mice in vivo through blocking IL-8/STAT3 signaling.ConclusionsIn summary, our findings suggested that GEN can inhibit the increased M2 polarization of macrophages and stemness of ovarian cancer cells by co-culture of macrophages with OCSLCs through disrupting IL-8/STAT3 signaling axis. This assisted GEN to be as a potential chemotherapeutic agent in human ovarian cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-1010-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Genistein inhibits stemness of SKOV3 cells induced by macrophages co-cultured with ovarian cancer stem-like cells through IL-8/STAT3 axis

Ning

Feng

Cao

et al. 2019

J Exp Clin Cancer Res

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“…Others showed that FBP induced oxidative stress in hepatic carcinoma cells, which caused an inhibition in proliferation, and this effect was suppressed when these cells were treated with anti-oxidants, such as N-acetyl-l-cysteine or catalase [12]. In contrast, using the same cell line, HepG2, FBP-treatment led to cell senescence, an increase in catalase activity [10] and a decrease in thiobarbituric acid reactive substances, which is a lipid peroxidation product and an indirect measure of radical oxygen species (ROS) [57]. Regardless of this discrepancy, there is a strong body of evidence suggesting that FBP has anti-oxidant properties [13] and, in the present study, FBP was able to increase expression of an antioxidant enzyme, SOD1, in FLF.…”

Section: Discussionmentioning

confidence: 99%

“…FBP has demonstrated anti-oxidant activity both in vitro and in vivo . However, conflicting results were also reported regarding this effect [10–13]. An earlier study found that activated liver myofibroblasts, or hepatic stellate cells, underwent a phenotype reversal associated with quiescence, decreased proliferation, and accumulation of lipid droplets when treated in vitro with FBP, all of which are characteristics of normal healthy fibroblast [14].…”

Section: Introductionmentioning

confidence: 99%

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

et al. 2019

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Pulmonary fibrosis (PF) is the result of chronic injury where fibroblasts become activated and secrete large amounts of extracellular matrix (ECM), leading to impaired fibroblasts degradation followed by stiffness and loss of lung function. Fructose-1,6-bisphosphate (FBP), an intermediate of glycolytic pathway, decreases PF development, but the underlying mechanism is unknown. To address this issue, PF was induced in vivo using a mouse model, and pulmonary fibroblasts were isolated from healthy and fibrotic animals. In PF model mice, lung function was improved by FBP as revealed by reduced collagen deposition and downregulation of ECM gene expression such as collagens and fibronectin. Fibrotic lung fibroblasts (FLF) treated with FBP for 3 days in vitro showed decreased proliferation, contraction, and migration, which are characteristic of myofibroblast to fibroblast phenotype reversal. ECM-related genes and proteins such as collagens, fibronectin and α-smooth muscle actin, were also downregulated in FBP-treated FLF. Moreover, matrix metalloproteinase (MMP) 1, responsible for ECM degradation, was produced only in fibroblasts obtained from healthy lungs (HLF) and FBP did not alter its expression. On the other hand, tissue inhibitor of metalloproteinase (TIMP)-1, a MMP1 inhibitor, and MMP2, related to fibroblast tissue-invasion, were predominantly produced by FLF and FBP was able to downregulate its expression. These results demonstrate that FBP may prevent bleomycin-induced PF development through reduced expression of collagen and other ECM components mediated by a reduced TIMP-1 and MMP2 expression.

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“…Ishikawa cells were seeded in 24‐well plates (1 × 10 4 cells per well) and incubated for 24 h before treatment. Cells were treated with F1,6 BP (Sigma‐Aldrich, USA) dissolved in fresh medium at concentrations of 150, 300, 600, and 1,250 μM (De Mesquita et al, 2013; Jost et al, 2018; Krause et al, 2017). As a positive control, cells were treated with 10 μM of cisplatin (CPPD; Fauldcispla®, Libbs Farmacêutica Ltda) (Thigpen et al, 2004).…”

Section: Methodsmentioning

confidence: 99%

Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells

Costa

Nassr

Diz

et al. 2020

J of Applied Toxicology

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Fructose‐1,6‐bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non‐cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro‐apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP‐treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53‐dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer.

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Fructose-1,6-bisphosphate decreases IL-8 levels and increases the activity of pro-apoptotic proteins in HepG2 cells

Cited by 11 publications

References 39 publications

RETRACTED ARTICLE: Genistein inhibits stemness of SKOV3 cells induced by macrophages co-cultured with ovarian cancer stem-like cells through IL-8/STAT3 axis

RETRACTED ARTICLE: Genistein inhibits stemness of SKOV3 cells induced by macrophages co-cultured with ovarian cancer stem-like cells through IL-8/STAT3 axis

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells

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