α‐Mangostin suppresses the de novo lipogenesis and enhances the chemotherapeutic response to gemcitabine in gallbladder carcinoma cells via targeting the AMPK/SREBP1 cascades

Shi, Yu; Fan, Yangwei; Hu, Yuan; Jing, Jiayu; Wang, Chuying; Wu, Yinying; Geng, Qing; Dong, Xuyuan; Li, Enxiao; Dong, Diansheng

doi:10.1111/jcmm.14785

Cited by 15 publications

(18 citation statements)

References 34 publications

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“…Student's t-test was used to analyse the comparison between two groups. 34 One-way ANOVA followed by Dunnett's test in GraphPad Prism version 5 (GraphPad Software, San Diego, CA, USA).…”

Section: Discussionmentioning

confidence: 99%

Mangiferin Inhibits Apoptosis and Autophagy Induced by Staphylococcus aureus in RAW264.7 Cells

Xu¹,

Yao²,

Wang³

et al. 2020

JIR

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Purpose Staphylococcus aureus ( S. aureus ) is an important bacterial pathogen, which creates infective inflammation to human being and animals. Mangiferin (MG) is one of the natural flavonoids with anti-inflammatory, anti-bacterial, and anti-oxidative properties. However, the anti-apoptosis and anti-autophagy of MG are unknown. Hence, this study was aimed to research the inhibition of MG on S. aureus -induced apoptosis and autophagy in RAW264.7 cells. Methods The RAW264.7 cells were pretreated with MG, or pretreated with SP600125 or anisomycin synchronously, and then infected with S. aureus (MOI=100:1). The viability and proliferation status of RAW264.7 cells were detected by MTT and EdU assay. The relative expression of TNF-α, IL-6 and IL-10 protein was tested with ELISA. The levels of Bax, Bcl-2, caspase-3, c-Jun N-terminal kinase (JNK), extracellular-regulated protein kinase (ERK), p38, LC3, Beclin-1, p62, phosphorylated JNK, phosphorylated p38 and phosphorylated ERK in cells were detected by Western blotting. The apoptosis rate of RAW264.7 cells was analyzed by flow cytometric assay. Results The study showed that MG significantly attenuated RAW264.7 cells apoptosis and autophagy caused by S. aureus . MG alleviated S. aureus -induced apoptosis by down-regulating the protein level of active caspase-3 and Bax and up-regulating the level of Bcl-2. MG also inhibited S. aureus -induced autophagy via decreasing the protein level of LC3-II/LC3-I and Beclin-1 or increasing the protein expression of p62. This protective role was dependent on the up-regulation of JNK signal pathway, which was confirmed by using JNK agonist and inhibitor. Conclusion Our results demonstrated that MG might protect RAW264.7 cells from S. aureus -induced apoptosis and autophagy via inhibiting JNK/Bax-dependent signal pathway. Therefore, MG may be a potential agent against pathological cell damage induced by S. aureus infection.

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“…Student's t-test was used to analyse the comparison between two groups. 34 One-way ANOVA followed by Dunnett's test in GraphPad Prism version 5 (GraphPad Software, San Diego, CA, USA).…”

Section: Discussionmentioning

confidence: 99%

Mangiferin Inhibits Apoptosis and Autophagy Induced by Staphylococcus aureus in RAW264.7 Cells

Xu¹,

Yao²,

Wang³

et al. 2020

JIR

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“…The proteins in conditioned medium were extracted as previously described [ 19 ]. Western blot assays and densitometric analysis of the resulting protein bands were performed as previously described [ 19 , 20 ]. For co-IP assays, GBC cells were lysed with lysis buffer, and the protein concentration of the cell lysates was determined by BCA quantitation.…”

Section: Methodsmentioning

confidence: 99%

Thrombospondin 4/integrin α2/HSF1 axis promotes proliferation and cancer stem-like traits of gallbladder cancer by enhancing reciprocal crosstalk between cancer-associated fibroblasts and tumor cells

Shi

Sun

Zhang

et al. 2021

J Exp Clin Cancer Res

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Background Cancer-associated fibroblasts (CAFs), the primary component of tumor stroma in tumor microenvironments, are well-known contributors to the malignant progression of gallbladder cancer (GBC). Thrombospondins (THBSs or TSPs) comprise a family of five adhesive glycoproteins that are overexpressed in many types of cancers. However, the expression and potential roles of TSPs in the crosstalk between CAFs and GBC cells has remained unclear. Methods Peritumoral fibroblasts (PTFs) and CAFs were extracted from GBC tissues. Thrombospondin expression in GBC was screened by RT-qPCR. MTT viability assay, colony formation, EdU incorporation assay, flow cytometry analysis, Transwell assay, tumorsphere formation and western blot assays were performed to investigate the effects of CAF-derived TSP-4 on GBC cell proliferation, EMT and cancer stem-like features. Subcutaneous tumor formation models were established by co-implanting CAFs and GBC cells or GBC cells overexpressing heat shock factor 1 (HSF1) to evaluate the roles of TSP-4 and HSF1 in vivo. To characterize the mechanism by which TSP-4 is involved in the crosstalk between CAFs and GBC cells, the levels of a variety of signaling molecules were detected by coimmunoprecipitation, immunofluorescence staining, and ELISA assays. Results In the present study, we showed that TSP-4, as the stromal glycoprotein, is highly expressed in CAFs from GBC and that CAF-derived TSP-4 induces the proliferation, EMT and cancer stem-like features of GBC cells. Mechanistically, CAF-secreted TSP-4 binds to the transmembrane receptor integrin α2 on GBC cells to induce the phosphorylation of HSF1 at S326 and maintain the malignant phenotypes of GBC cells. Moreover, the TSP-4/integrin α2 axis-induced phosphorylation of HSF1 at S326 is mediated by Akt activation (p-Akt at S473) in GBC cells. In addition, activated HSF1 signaling increased the expression and paracrine signaling of TGF-β1 to induce the transdifferentiation of PTFs into CAFs, leading to their recruitment into GBC and increased TSP-4 expression in CAFs, thereby forming a positive feedback loop to drive the malignant progression of GBC. Conclusions Our data indicate that a complex TSP-4/integrin α2/HSF1/TGF-β cascade mediates reciprocal interactions between GBC cells and CAFs, providing a promising therapeutic target for gallbladder cancer patients.

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“…27,28 α-M could enhance the chemotherapeutic response in gallbladder carcinoma cells. 29 Next, the mechanism by which α-M could trigger autophagy to enhance the chemosensitivity of GC cells was investigated. A previous investigation revealed that aberrant STAT3 expression is associated with neoplastic growth, metastasis, and prognosis; it is also involved in autophagic regulation, which may in turn contribute to tumor chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

The effects and mechanism of α‐mangostin on chemosensitivity of gastric cancer cells

Zeng

2021

The Kaohsiung J of Med Scie

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This work investigated the effect of α-mangostin (α-M) on gastric cancer (GC) cell chemoresistance and its underlying mechanisms. Different concentrations of α-M and CDDP were applied to treat GC cells (SGC7901) and CDDP-resistant GC cells (SGC7901/CDDP) for 24 or 48 h. CCK-8 assays were used to measure the inhibitory effect of CDDP or α-M on SGC7901 and SGC7901/CDDP cells as well as the halfmaximal inhibitory concentrations (IC50) of α-M for SGC7901 and SGC7901/CDDP cells. The optimal concentration and induction time of CDDP or α-M were determined. SGC7901/CDDP cells were treated with CDDP or/and α-M, where some of them were transfected with pcDNA3.1 or pcDNA3.1-EBI3. Cell proliferation and apoptosis were assessed as well as the levels of EBI3, STAT3, p-STAT3, autophagyrelated proteins, and apoptosis-related proteins. CDDP inhibited SGC7901 cell proliferation in a dose-dependent manner. The IC50 of α-M for SGC7901 cells was 12.86 μM and that for SGC7901/CDDP cells was 13.69 μM. The optimal concentrations of CDDP and α-M for SGC7901/CDDP cells were 2 and 15 μM, respectively, and the optimal time was 48 h. The SGC7901/CDDP cells in the CDDP+/α-M+ group had elevated inhibition of proliferation and apoptosis rates. Western blot analysis revealed enhanced levels of LC3-II/I and Beclin1, reduced p62 level, decreased Bcl2 level, and increased levels of Bax and cleaved caspase-3/9. The EBI3/STAT3 pathway was implicated in the effect of α-M on SGC7901/CDDP cell development. α-M increases the chemosensitivity of GC cells by facilitating autophagy and inactivating the EBI3/STAT3 pathway.

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α‐Mangostin suppresses the de novo lipogenesis and enhances the chemotherapeutic response to gemcitabine in gallbladder carcinoma cells via targeting the AMPK/SREBP1 cascades

Cited by 15 publications

References 34 publications

<p>Mangiferin Inhibits Apoptosis and Autophagy Induced by <em>Staphylococcus aureus</em> in RAW264.7 Cells</p>

<p>Mangiferin Inhibits Apoptosis and Autophagy Induced by <em>Staphylococcus aureus</em> in RAW264.7 Cells</p>

Thrombospondin 4/integrin α2/HSF1 axis promotes proliferation and cancer stem-like traits of gallbladder cancer by enhancing reciprocal crosstalk between cancer-associated fibroblasts and tumor cells

The effects and mechanism of α‐mangostin on chemosensitivity of gastric cancer cells

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