Astragalus Polysaccharides Inhibits Tumorigenesis and Lipid Metabolism Through miR-138-5p/SIRT1/SREBP1 Pathway in Prostate Cancer

Guo, Shuai; Ma, Ben; Jiang, Xingkang; Li, Xiaojiang; Jia, Yulin

doi:10.3389/fphar.2020.00598

Cited by 45 publications

(24 citation statements)

References 31 publications

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“…Fatty acid and cholesterol metabolism are dysregulated in most patients with advanced PC. 18,19 Previous studies have shown a positive association between serum cholesterol levels and high-grade prostate cancer. 6,20 Prostate cancer can take in exogenous cholesterol through SR-B1 and synthesize endogenous cholesterol from acetyl-CoA.…”

Section: Discussionmentioning

confidence: 99%

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

Huang

Dai

et al. 2021

OTT

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Background: Almost all metastatic hormone-sensitive prostate cancers (mHSPC) will develop into metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT). The expression level of squalene monooxygenase (SQLE) is increased in CRPC cells and regulates cholesterol metabolism. This study verified the biological function and mechanisms of SQLE in CRPC. Methods: The expression of SQLE in human prostate cancer cells was overexpressed or silenced and its efficacy on cell survival was determined by the MTS test. Energy metabolism phenotype test was evaluated by XF real-time ATP rate assay, XF cell mitochondrial stress test, XF glycolysis stress test and XF mito fuel flex test. Cell migration and invasion were evaluated by colony formation assays and transwell assays; the expression of mRNA and protein was assessed by RT-qPCR and Western blot, respectively. Moreover, BALB/c nude mice model was performed to evaluate the lymph node metastasis. Results: In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide. Conclusion:Our study revealed that SQLE is involved in the progression of castration resistance in CRPC through mediating metabolic reprogramming, presenting SQLE as a new target for the treatment of mCRPC.

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Section: Discussionmentioning

confidence: 99%

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

Huang

Dai

et al. 2021

OTT

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“…We found that 3 mg/ml APS supplementation remarkably increased the TAG level in flies, but it did not significantly affect the food consumption. Previous research has showed that APS can inhibit lipid metabolism via miR-138-5p/SIRT1/SREBP1 pathways in prostate cancer [ 28 ] and improve lipid metabolism disorders in diabetic hamsters [ 29 ]. In silkworm, APS did not affect food intake [ 25 ], which was consistent with our results.…”

Section: Discussionmentioning

confidence: 99%

Extension of Drosophila Lifespan by Astragalus polysaccharide through a Mechanism Dependent on Antioxidant and Insulin/IGF-1 Signaling

Yang

Xiu

Yang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Historical literature and pharmacological studies demonstrate that Astragalus polysaccharide (APS) has anti-inflammatory and antioxidative effects. Studies into the longevity effects of APS are limited, and the molecular mechanism of lifespan extension by APS is not elucidated yet. Here, the longevity effect of APS was investigated in Drosophila melanogaster by feeding dose-dependent APS. APS significantly extended the lifespan and improved the reproduction. Meanwhile, APS increased locomotion, TAG level, and starvation resistance and reduced the mortality rate induced by hydrogen peroxide. The activities of superoxide dismutase (SOD) and catalase (CAT) were increased in flies treated with APS diet. Moreover, APS significantly enhanced expressions of antioxidant genes (Sod1, Sod2, and Cat), dFoxO, and 4E − BP, decreased the expressions of insulin-like peptides (dilp2, dilp3, and dilp5), and longevity gene MTH. Together, these results indicate that APS can prolong the lifespan by regulating antioxidant ability and insulin/IGF-1 signaling and also enhance the reproduction ability in Drosophila. APS may be explored as a novel agent for slowing the aging process and improving reproduction.

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“…In addition to licorice, the drug active ingredients of astragalus and Polygonatum could regulate the expression of ESR1 and MAPK14 in the merge network. It has been reported that licorice, astragalus, and Polygonatum can inhibit tumorigenesis in prostate cancer [30][31][32][33]. ESR1 is signi cantly up-regulated in androgen-deprived prostate cancer and promotes tumor cell proliferation [34].…”

Section: Discussionmentioning

confidence: 99%

Identification of the active substance and mechanisms of CFF-1 for treatment of prostate cancer based on network pharmacology, virtual screening, and molecular dynamics simulation

dai¹,

Liu²

2021

Preprint

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Background CFF-1 is an effective treatment option for prostate cancer patients, but there is a lack of network pharmacology research on its molecular mechanism. Methods Based on bioavailability and drug-likeness, the main active ingredients of CFF-1 were obtained through the Traditional Chinese Medicine System Pharmacology (TCMSP) database. The GeneCard, OMIM, PharmGKB, Therapeutic Targets database, and DrugBank were used to construct prostate cancer target gene sets. Construct an ingredients-target network and a protein-protein interaction network respectively, and GO and KEGG enrichment analysis were performed. After merging the two networks, important target genes were obtained in the merged network, and virtual screening of CFF-1 active ingredients was performed on these important target genes. Then the dynamic process of the binding of two small drug molecules to the target protein was simulated by molecular dynamics. Results 112 active ingredients of CFF-1 and 206 prostate cancer target genes were identified. The results of GO and KEGG enrichment analysis showed that the target genes regulated by CFF-1 were involved in prostate cancer-related signaling pathways. Two important target genes were obtained in the merge network, as well as the small molecules with the best binding among the active ingredients of CFF-1 were obtained through a virtual screening tool developed by us. Finally, simulate the dynamic process of two small molecules binding to the target protein. Conclusion In conclusion, this study predicted the potential molecular mechanism of CFF-1 in the treatment of prostate cancer through network pharmacology and found important target genes and their active ingredients in CFF-1. This provided a direction for future research on CFF-1 and promoted the reasonable application of CFF-1 in the clinical treatment of prostate cancer.

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Astragalus Polysaccharides Inhibits Tumorigenesis and Lipid Metabolism Through miR-138-5p/SIRT1/SREBP1 Pathway in Prostate Cancer

Cited by 45 publications

References 31 publications

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

Extension of Drosophila Lifespan by Astragalus polysaccharide through a Mechanism Dependent on Antioxidant and Insulin/IGF-1 Signaling

Identification of the active substance and mechanisms of CFF-1 for treatment of prostate cancer based on network pharmacology, virtual screening, and molecular dynamics simulation

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