α, γ-Mangostins Induce Autophagy and Show Synergistic Effect with Gemcitabine in Pancreatic Cancer Cell Lines

Kim, Myoungjae; Chin, Young‐Won

doi:10.4062/biomolther.2017.074

Cited by 19 publications

(10 citation statements)

References 55 publications

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“…As shown in Figure 1A,B, MA repressed the growth of GBC cells in a time-and dose-dependent manner. The half-maximum inhibitory concentrations of MA were approximately 5 μmol/L in the NOZ and GBC-SD cells, which were similar to previous results and did not have cytotoxic effects in normal bile duct epithelial cell lines (HIBEC, as shown in Figure S1) 21 ; thus, we selected 5 μmol/L MA for the subsequent experiments. To interrogate the effects of MA on the proliferation of GBC cells, NOZ and GBC-SD cells were treated with 5 μmol/L MA to evaluate colony formation.…”

Section: α-Mangostin Suppresses Proliferation and Induces Apoptosissupporting

confidence: 83%

“…21,22 In addition, α-mangostin kills cancer cells by inducing cell cycle arrest, apoptosis and autophagic cell death; moreover, α-mangostin suppresses oxidation, invasion and metastasis of several types of cancer. 21 However, the molecular mechanisms of the effects of α-mangostin in GBC cells have not yet been reported. Interestingly, α-mangostin triggers the autophagy-related cell death of glioblastoma cells by activating AMPK (AMP-activated protein kinase).…”

Section: Introductionmentioning

confidence: 99%

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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

Shi

Fan

et al. 2019

J Cellular Molecular Medi

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High rates of de novo lipid synthesis have been discovered in certain kinds of tumours, including gallbladder cancer (GBC). Unlike several other tumours, GBC is highly insensitive to standard adjuvant therapy, which makes its treatment even more challenging. Although several potential targets and signalling pathways underlying GBC chemoresistance have been revealed, the precise mechanisms are still elusive. In this study, we found that α‐Mangostin, as a dietary xanthone, repressed the proliferation and clone formation ability, induced cell cycle arrest and the apoptosis, and suppressed de novo lipogenesis of gallbladder cancer cells. The underlying mechanisms might involve the activation of AMPK and, therefore, the suppression of SREBP1 nuclear translocation to blunt de novo lipogenesis. Furthermore, SREBP1 silencing by siRNA or α‐mangostin enhanced the sensitivity of gemcitabine in gallbladder cancer cells. In vivo studies also displayed that MA or gemcitabine administration to nude mice harbouring NOZ tumours can reduce tumour growth, and moreover, MA administration can significantly potentiate gemcitabine‐induced inhibition of tumour growth. Corroborating in vitro findings, tumours from mice treated with MA or gemcitabine alone showed decreased levels of proliferation with reduced Ki‐67 expression and elevated apoptosis confirmed by TUNEL staining, furthermore, the proliferation inhibition and apoptosis up‐regulation were obviously observed in MA combined with gemcitabine treatment group. Therefore, inhibiting de novo lipogenesis via targeting the AMPK/SREBP1 signalling by MA might provide insights into a potential strategy for sensitizing GBC cells to chemotherapy.

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Section: α-Mangostin Suppresses Proliferation and Induces Apoptosissupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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

Fan

et al. 2019

J Cellular Molecular Medi

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“…Furthermore, biofabricated silver nanoparticle containing water extract of mangosteen bark was reported to preferentially killed A549 lung cancer cells (Zhang & Xiao, 2018). In addition, Kim, Chin & Lee (2017) showed that the mixture of α- and γ-mangostin can inhibit pancreatic cancer cell lines. Their action were contributed by possible autophagy development via AMP-activated protein kinase/mTOR and p38 pathways (Kim, Chin & Lee, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, Kim, Chin & Lee (2017) showed that the mixture of α- and γ-mangostin can inhibit pancreatic cancer cell lines. Their action were contributed by possible autophagy development via AMP-activated protein kinase/mTOR and p38 pathways (Kim, Chin & Lee, 2017). Interestingly, both compounds, together with a common drug called gemcitabine, were also found to synergistically inhibit the cancer cells (Kim, Chin & Lee, 2017), highlighting possible drug concoction for better treatment efficacy.…”

Section: Introductionmentioning

confidence: 99%

Recent updates on metabolite composition and medicinal benefits of mangosteen plant

Aizat¹,

Jamil²,

Ahmad-Hashim³

et al. 2019

PeerJ

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Background Mangosteen (Garcinia mangostana L.) fruit has a unique sweet-sour taste and rich in beneficial compounds such as xanthones. Mangosteen has been originally used in various folk medicines to treat diarrhea, wound, and fever. More recently, it has been used as a major component in health supplement products for weight loss and promoting general health. This is perhaps due to its known medicinal benefits including as anti-oxidant and anti-inflammation. Interestingly, the publications related to mangosteen has surged in recent years suggesting its popularity and usefulness in research laboratories. However, there is still no updated reviews (up to 2018) in this booming research area, particularly on its metabolite composition and medicinal benefits. Method In this review, we have covered recent articles within the year of 2016 to 2018, which focuses on several aspects including the latest findings on compound composition from mangosteen fruit as well as its medicinal usages. Result Mangosteen has been vastly used in medicinal areas including as anti-cancer, anti-microbial, and anti-diabetes treatments. Furthermore, we have also described the benefits of mangosteen extract in protecting various human organs such as liver, skin, joint, eye, neuron, bowel, and cardiovascular tissues against disorders and diseases. Conclusion All in all, this review describes the numerous manipulations of mangosteen extracted compounds in medicinal areas and highlights the current trend of its research. This will be important for future directed research and may allow researchers to tackle the next big challenge in mangosteen study; drug development and human applications.

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“…9 Previous studies have demonstrated that α-M has a number of biological activities, including antibacterial, 10 cardioprotective, 11 neuroprotective, 12 and anticancer effects. 13,14 The antitumor effects of α-M regulate the proliferation and apoptosis of GC cells and have been implicated in diverse activities, including modulation of autophagy. 15 However, the molecular mechanism of α-M in autophagy and chemotherapeutic drug resistance in GC cells have not been fully elucidated.…”

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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, γ-Mangostins Induce Autophagy and Show Synergistic Effect with Gemcitabine in Pancreatic Cancer Cell Lines

Cited by 19 publications

References 55 publications

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

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

Recent updates on metabolite composition and medicinal benefits of mangosteen plant

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

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