Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation

Fan, Yonggang; Weng, Zhiyong; Gao, Hongguo; Hu, Jiehua; Wang, Hongyan; Li, Lihua; Liu, Hua

doi:10.1371/journal.pone.0145790

Cited by 12 publications

(12 citation statements)

References 34 publications

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“…However, the inhibitory effect of IAL on the phosphorylation of JNK and p38 MAPK was not significant. It was reported that IAL could overcome resistance to radiation in UMSCC-10A cells by specifically inhibiting the activation of the Erk1/2 signaling pathway [39]. The MAPKs are activated by phosphorylation caused by specific MAP kinase kinases (MKKs), which, in turn, are activated by MKK kinases [40].…”

Section: Discussionmentioning

confidence: 99%

Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury

Ding

Song

et al. 2018

Acta Pharmacol Sin

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Isoalantolactone (IAL) is a sesquiterpene lactone extracted from roots of Inula helenium L and has shown anti-inflammatory effects. In this study we investigated the therapeutic effects of IAL on acute lung injury (ALI) and elucidated the mechanisms underlying its anti-inflammation potential in vitro and in vivo. Treatment with lipopolysaccharide (LPS, 100 ng/mL) drastically stimulated production of inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6 in mouse bone marrow-derived macrophages (BMDMs), which was dose-dependently suppressed by pretreatment with IAL (2.5, 5, 10, 20 μM). We further revealed that IAL suppressed LPS-induced NF-κB, ERK, and Akt activation. Moreover, the downregulation of non-degradable K63-linked polyubiquitination of TRAF6, an upstream transcription factor of NF-κB, contributed to the anti-inflammatory effects of IAL. ALI was induced in mice by intratracheal injection of LPS (5 mg/kg). Administration of IAL (20 mg/kg, i.p.) significantly suppressed pulmonary pathological changes, neutrophil infiltration, pulmonary permeability, and pro-inflammatory cytokine expression. Our results demonstrate that IAL is a potential therapeutic reagent against inflammation and ALI.

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Section: Discussionmentioning

confidence: 99%

Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury

Ding

Song

et al. 2018

Acta Pharmacol Sin

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“…Experiments have shown that IATL can induce a highly selective cytotoxic effect, while its toxicity to the body's normal peripheral blood lymphocytes is very low . The antitumor properties of IATL in lung and breast cancers have already been reported . However, the effects of IATL in GBM have not yet been confirmed.…”

Section: Introductionmentioning

confidence: 99%

Isoalantolactone inhibits IKKβ kinase activity to interrupt the NF‐κB/COX‐2‐mediated signaling cascade and induces apoptosis regulated by the mitochondrial translocation of cofilin in glioblastoma

et al. 2019

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Isoalantolactone (IATL), a sesquiterpene lactone compound, possesses many pharmacological and biological activities, but its role in glioblastoma (GBM) treatment is still unknown. The aim of the current study was to investigate the antiglioma effects of IATL and to explore the underlying molecular mechanisms. In the current study, the biological functions of IATL were examined by MTT, cell migration, colony formation, and cell apoptosis assays. Confocal immunofluorescence techniques, chromatin immunoprecipitation, and pull‐down assays were used to explore the precise underlying molecular mechanisms. To examine IATL activity and the molecular mechanisms by which it inhibits glioma growth in vivo, we used a xenograft tumor mouse model. Furthermore, Western blotting was used to confirm the changes in protein expression after IATL treatment. According to the results, IATL inhibited IKKβ phosphorylation, thus inhibiting both the binding of NF‐κB to the cyclooxygenase 2 (COX‐2) promoter and the recruitment of p300 and eventually inhibiting COX‐2 expression. In addition, IATL induced glioma cell apoptosis by promoting the conversion of F‐actin to G‐actin, which in turn activates the cytochrome c (Cyt c) and caspase‐dependent apoptotic pathways. In the animal experiments, IATL reduced the size and weight of glioma tumors in xenograft mice and inhibited the expression of COX‐2 and phosphorylated NF‐κB p65 in the transplanted tumors. In conclusion, the current study indicated that IATL inhibited the expression of COX‐2 through the NF‐κB signaling pathway and induced the apoptosis of glioma cells by increasing actin transformation. These results suggested that IATL could be greatly effective in GBM treatment.

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“…One of our main discovery was that FTO protein levels in the pancreas were associated with energy intake: low on low energy diet and high on high energy diet, compared to normal diet. Earlier in vitro studies showed that FTO overexpression in MIN6 (mouse insulinoma) cells significantly inhibited insulin secretion in the presence of glucose, but did not affect insulin expression 47 . As a result, we argue that increased FTO levels in the pancreas may directly influence insulin release from beta cells.…”

Section: Discussionmentioning

confidence: 99%

“…The distribution of Fto mRNA and protein levels was previously studied by several research groups, primarily using rodent models 26 , 29 , 31 , 42 , 47 – 49 . The role of Fto in rodents is, however, limited as compared to humans.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, we argue that increased FTO levels in the pancreas may directly influence insulin release from beta cells. Moreover, FTO overexpression in the pancreas resulting from a high energy diet might also be a consequence of the reactive oxygen species (ROS) production and activation of the NF-κB pathway 47 . This hypothesis is plausible, because at early stages of T2D, pancreatic secretion is increased in response to the decreased number of insulin receptors in peripheral tissues and increased basal level of glucose in the blood 47 .…”

Section: Discussionmentioning

confidence: 99%

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Intracellular and tissue specific expression of FTO protein in pig: changes with age, energy intake and metabolic status

Ferenc

Pilžys

Garbicz

et al. 2020

Sci Rep

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Genome-wide association studies in the FTO gene have identified SNPs correlating with obesity and type 2 diabetes. In mice, lack of Fto function leads to intrauterine growth retardation and lean phenotype, whereas in human it is lethal. The aim of this study in a pig model was to determine the localization of the FTO protein in different tissues and cell compartments, in order to investigate potential targets of FTO action. To better understand physiological role of FTO protein, its expression was studied in pigs of different age, metabolic status and nutrition, using both microscopic methods and Western blot analysis. For the first time, FTO protein was found in vivo in the cytoplasm, of not all, but specific tissues and cells e.g. in the pancreatic β-cells. Abundant FTO protein expression was found in the cerebellum, salivary gland and kidney of adult pigs. No FTO protein expression was detected in blood, saliva, and bile, excluding its role in cell-to-cell communication. In the pancreas, FTO protein expression was positively associated with energy intake, whereas in the muscles it was strictly agerelated. In IUGR piglets, FTO protein expression was much higher in the cerebellum and kidneys, as compared to normal birth body weight littermates. In conclusion, our data suggest that FTO protein may play a number of distinct, yet unknown intracellular functions due to its localization. Moreover, it may play a role in animal growth/development and metabolic state, although additional studies are necessary to clarify the detailed mechanism(s) of action. Genome-wide association studies (GWAS) have shown that single nucleotide polymorphisms (SNPs) in intron 1 of the FTO (Fat mass and obesity associated) gene are strongly correlated with an increased risk of obesity in humans 1-4. In the human FTO gene, the mutation (alteration p. Arg316 Gln) that inhibits catalytic activity of the protein, results in an autosomal recessive lethal syndrome 5. In Fto knockout mice, body weight and fat mass decrease 6 , while in animals overexpressing FTO they increase 7. Evidence from genetic epidemiology studies, life-course modeling, and diet-induced fetal programming data suggests that the FTO gene plays an important role in these complex biological interactions. It may provide the missing link in the developmental regulation of energy metabolism. The FTO variants associated with intrauterine growth retardation (IUGR) and, in consequence, low birth weight, confer a predisposition to obesity later in life. This finding favors the hypothesis of the existence of a common genetic denominator that predisposes to low birth weight and obesity in adults 8-10. Specifically, Fto deletion caused delayed growth, decreased white body fat, increased energy metabolism, and systemic sympathetic activation 6. For example, in wild-type mice, fasting reduced Fto mRNA levels and the number of Fto-immunoreactive cells in the hypothalamus. Interestingly, glucose treatment reversed this effect 11. However, another group of researchers showed that palatable ...

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Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation

Cited by 12 publications

References 34 publications

Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury

Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury

Isoalantolactone inhibits IKKβ kinase activity to interrupt the NF‐κB/COX‐2‐mediated signaling cascade and induces apoptosis regulated by the mitochondrial translocation of cofilin in glioblastoma

Intracellular and tissue specific expression of FTO protein in pig: changes with age, energy intake and metabolic status

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