β‐asarone inhibited cell growth and promoted autophagy via P53/Bcl‐2/Bclin‐1 and P53/AMPK/mTOR pathways in Human Glioma U251 cells

Wang, Nanbu; Zhang, Qinxin; Luo, Lan; Ning, Baile; Fang, Yongqi

doi:10.1002/jcp.26118

Cited by 60 publications

(48 citation statements)

References 38 publications

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“…37,38 Furthermore, a number of natural compounds have been found to modulate autophagy via this signaling pathway. 40 Consistently, we demonstrated that activation of the AMPK/mTOR signaling pathway was involved in XAG mediated induction of autophagy, as well as its antimetastatic and anti-EMT effects. 39 In human Glioma U251 cells, β-asarone induced autophagic cell death through activation of the P53/Bcl-2/ Beclin-1 and P53/AMPK/mTOR pathways.…”

Section: Discussionsupporting

confidence: 63%

“…39 In human Glioma U251 cells, β-asarone induced autophagic cell death through activation of the P53/Bcl-2/ Beclin-1 and P53/AMPK/mTOR pathways. 40 Consistently, we demonstrated that activation of the AMPK/mTOR signaling pathway was involved in XAG mediated induction of autophagy, as well as its antimetastatic and anti-EMT effects. XAG significantly increased p-AMPK level in a dose-dependent manner and simultaneously decreased p-mTOR expression.…”

Section: Discussionsupporting

confidence: 63%

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Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Yang

Xie

Liu

et al. 2019

Cell Biochemistry & Function

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Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti-metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3-methyadenine (3-MA) or knockdown of the pro-autophagy Beclin-1 effectively abrogated the XAG-induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p-AMPK while decreasing p-mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy-mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti-metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti-tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti-metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC. KEYWORDSAMPK/mTOR, autophagy, HCC, metastasis, xanthoangelol Xiuwei Yang and Jing Xie are co-first authors and contributed equally to this work.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionsupporting

confidence: 63%

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Yang

Xie

Liu

et al. 2019

Cell Biochemistry & Function

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“…p53 is a major tumor suppressor gene that acts an important part in boosting apoptosis of cancer cells . In addition, research has shown that p53 can both promote apoptosis and inhibit apoptosis, and is a double‐face transcription factor .…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity, genotoxicity, oxidative stress, and apoptosis in HepG2 cells induced by the imidazole ionic liquid 1‐dodecyl‐3‐methylimidazolium chloride

Wang

Wan

Huo

et al. 2020

Environmental Toxicology

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This study purposes to assess the cytotoxicity of 1-dodecyl-3-methylimidazolium chloride ([C 12 min]Cl) in human hepatocellular carcinoma (HepG2) cells. To this end, HepG2 cells were exposed to a range concentration of [C 12 min]Cl and evaluated cell viability, genotoxicity, oxidative stress, apoptosis, cell cycle, and apoptosis-related gene expression to determine cytotoxicity. The outcomes showed that [C 12 min]Cl curbed HepG2 cell growth and reduced cell viability in a concentration-and time-dependent manner.Moreover, our assay results also revealed that exposure to [C 12 min]Cl prompted DNA damage and apoptosis, reduced SOD and GSH content, enhanced MDA level, and changed the cell cycle of HepG2 cells. In addition, [C 12 min] Cl caused alters in the expression levels of p53, Bax, and Bcl-2, indicating that p53 and Bcl-2 family may be involved in the cytotoxicity and apoptosis of HepG2 cells induced by [C 12 min]C1. In summary, these results indicate that [C 12 min]Cl exerts genotoxicity, physiological toxicity and prompts apoptosis in HepG2 cells, and is not an alleged green solvent. K E Y W O R D S apoptosis, cytotoxicity, genotoxicity, ionic liquids, oxidative stress 1 | INTRODUCTION Ionic liquids (ILs) are low melting organic salts at room temperature and are considered a green substitute for industrial volatile organic compounds. 1-3 They are composed of various cations and anions, for example, imidazolium, pyridinium, bromide (Br − ), and chloride (Cl − ). 4 Last several years, ILs have drawn wide attention owing to their unique excellent physical and chemical properties, such as low vapor pressure and nonvolatility, 5,6 good thermal and chemical stability, 7,8and relatively high viscosity. 9 These ILs as environmentally friendly chemicals are famous mainly because their vapor pressure is negligible compared to many inorganic and organic materials. 5,10 Due to their unique properties, ILs are currently being used in a diverse range of applications, including ecology, 11,12 chemical engineering, 13 the medical field, 14 food industry, 15 textiles, 16 and electrochemistry. 17 However, many studies have shown that ILs may be released into aquatic environments via effluent discharges and accidental spills and cause damage to aquatic organisms. 18,19 For example, IL toxicity has been evaluated in microalgae, 20 fish, 21,22 and in Daphnia magna. 23 In addition, several previous studies also showed that ILs are cytotoxic to many classes of cells, such as the human HeLa cell line, 24 and PC12 cells. 25 In contrast, limited information is available on the toxic mechanism of ILs, which is important in risk evaluation.The human hepatocellular carcinoma (HepG2) cell line was derived from a hepatoblastoma at first and retains the structural and functional polarity that hepatocytes exhibit in vivo. 26 It plays a key role in the activation/detoxification of genotoxic procarcinogens and reflects the metabolism of such compounds in vivo better than experimental models with metabolically incompetent cells and exog...

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“…Association of the expression level of miR-374a with clinicopathological factors of glioma. it was reported that the mTOR pathway is a crucial signaling pathway involved in the development of glioma (38). In addition, four hub genes, CCND1, SP1, CDK6 and CDK4, were identified from the PPI of predicted target genes of miR-374a, which may be directly or indirectly involved in the development of glioma.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

et al. 2019

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Certain microRNAs (miRNAs/miRs) may be used as prognostic biomarkers in various types of cancer. The purpose of the present study was to identify miRNAs that were abnormally expressed in glioma of different grades, and to evaluate their clinical implications in patients with glioma. The differentially expressed miRNAs were evaluated from the expression profiles of six glioma tissues (three low-grade and three high-grade gliomas) determined using a microarray platform. Reverse transcription-quantitative polymerase chain reaction analysis was used to further verify the aberrant expression of the candidate miRNA in a set of 42 patients and 5 healthy controls. The miRNA target genes were predicted and the protein-protein interaction network was generated; furthermore, functional enrichment analysis of the target genes in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed. Kaplan-Meier curves and Log-rank analysis, as well as multivariate Cox regression analysis were performed to assess the association of the candidate miRNA with patient survival. A total of 15 differentially expressed miRNAs, including 13 downregulated and 2 upregulated miRNAs, were identified by comparison of low-grade and high-grade glioma tissues. The miR-374a expression of high-grade gliomas was significantly lower than that of low-grade gliomas (fold change, -4.43; P=0.027). The expression levels of miR-374a gradually decreased with the increase of the pathological grade of glioma. Pearson's Chi-square test was used to determine the association of miR-374a expression with several clinicopathological factors. Furthermore, low expression of miR-374a was determined to be an independent prognostic marker and that it was significantly associated with overall survival (P=0.0213). GO and KEGG pathway analysis revealed that the target genes of miR-374a may be involved in the regulation of the RNA polymerase II promoter and mTOR signaling pathway. The four hub genes (CCND1, SP1, CDK4, CDK6) were also identified by PPI network analysis. In conclusion, the present study indicated that miR-374a may be used as a promising prognostic biomarker for the screening of high-risk populations and for the assessment of the prognosis of patients with glioma.

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β‐asarone inhibited cell growth and promoted autophagy via P53/Bcl‐2/Bclin‐1 and P53/AMPK/mTOR pathways in Human Glioma U251 cells

Cited by 60 publications

References 38 publications

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Cytotoxicity, genotoxicity, oxidative stress, and apoptosis in HepG2 cells induced by the imidazole ionic liquid 1‐dodecyl‐3‐methylimidazolium chloride

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

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