PTP1B inhibitors from the seeds of Iris sanguinea and their insulin mimetic activities via AMPK and ACC phosphorylation

Yang, Jianmei; Ha, Thi Kim Quy; Lee, Ba-Wool; Kim, Jinwoong; Oh, Won Keun

doi:10.1016/j.bmcl.2017.09.031

Cited by 26 publications

(21 citation statements)

References 33 publications

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“…2e and 4e, the knockdown and pharmacological inhibition of PTP1B both induced G0/G1 phase cell cycle arrest in PDAC cell lines, which was an obvious manifestation of AMPK activation. Previous studies have demonstrated that loss of PTP1B protects against metabolic diseases such as myocardial anomalies, atherosclerotic plaque formation and diabetes by activating AMPK [33][34][35] , further confirming the correlation and interaction between PTP1B and AMPK. Subsequently, we found that AMPK activation appears to exert its antitumor effects through p70S6K inhibition in vitro (Fig.…”

Section: Discussionsupporting

confidence: 60%

Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway

et al. 2019

Cell Death Dis

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Pancreatic cancer is a highly malignant cancer and lacks effective therapeutic targets. Protein-tyrosine phosphatase 1B (PTP1B), a validated therapeutic target for diabetes and obesity, also plays a critical positive or negative role in tumorigenesis. However, the role of PTP1B in pancreatic cancer remains elusive. Here, we initially demonstrated that PTP1B was highly expressed in pancreatic tumors, and was positively correlated with distant metastasis and tumor staging, and indicated poor survival. Then, inhibition of PTP1B either by shRNA or by a specific small-molecule inhibitor significantly suppressed pancreatic cancer cell growth, migration and colony formation with cell cycle arrest in vitro and inhibited pancreatic cancer progression in vivo. Mechanism studies revealed that PTP1B targeted the PKM2/ AMPK/mTOC1 signaling pathway to regulate cell growth. PTP1B inhibition directly increased PKM2 Tyr-105 phosphorylation to further result in significant activation of AMPK, which decreased mTOC1 activity and led to inhibition of p70S6K. Meanwhile, the decreased phosphorylation of PRAS40 caused by decreased PKM2 activity also helped to inhibit mTOC1. Collectively, these findings support the notion of PTP1B as an oncogene and a promising therapeutic target for PDAC.

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Section: Discussionsupporting

confidence: 60%

Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway

et al. 2019

Cell Death Dis

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“…Most plant parts of I. sanguinea cultivars also have medicinal value. Rhizomes and roots are often used for reducing inflammation and detoxification; triterpenes from seeds can regulate glucose uptake and thus beneficial to treat metabolic disorders such as diabetes 3 – 5 . Despite the significant features of I. sanguinea , its cultivation and utilization are not well established in China 1 , 3 , 6 .…”

Section: Introductionmentioning

confidence: 99%

Establishment of an efficient in vitro propagation system for Iris sanguinea

Wang

Rahman

et al. 2018

Sci Rep

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Iris sanguinea is a perennial flowering plant that is typically cultivated through seeds or bulbs. However, due to limitations in conventional propagation, an alternate regeneration system using seeds was developed. The protocol included optimization of sterilization, stratification and scarification methods as iris seeds exhibit physiological dormancy. In addition to chlorine-based disinfection, alkaline or heat treatment was used to break seed dormancy and reduce contamination. When seeds were soaked in water at 80 °C overnight, and sterilized with 75% EtOH for 30 s and 4% NaOCl solution for 20 minutes, contamination was reduced to 10% and a 73.3% germination was achieved. The germinated seedlings with 2-3 leaves and radicle were used as explants to induce adventitious buds. The optimal MS medium with 0.5 mg L−1 6-benzylaminopurine, 0.2 mg L−1 NAA, and 1.0 mg L−1 kinetin resulted in 93.3% shoot induction and a proliferation coefficient of 5.30. Medium with 0.5 mg L−1 NAA achieved 96.4% rooting of the adventitious shoots. The survival rate was more than 90% after 30 days growth in the cultivated matrix. In conclusion, a successful regeneration system for propagation of I. sanguinea was developed using seeds, which could be utilized for large-scale propagation of irises of ecological and horticultural importance.

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“…To determine the level of glucose uptake into 3T3-L1 adipocytes, a fluorescent derivative of glucose (2-NBDG) (Invitrogen, OR, USA) was used as previously described with slight modifications 34,37 . First, 3T3-L1 preadipocytes were differentiated by Dulbecco’s Modified Eagle’s Medium (DMEM) (HyClone, IL, USA) containing 10% fetal bovine serum (FBS) (Gibco, NY, USA), 1 μ M dexamethasone (Sigma, MO, USA), 520 μ M 3-isobutyl-1-methyl-xanthine (Sigma, MO, USA) and 1 μ g/mL insulin (Roche, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…PTP1B enzyme (human, recombinant) was purchased from BIOMOL International LP (USA) and the enzyme assay was performed as previously described 34 . Briefly, the assay was performed in 96-well plate containing 4 mM p -NPP and PTP1B (0.05–0.1 μ g) in enzyme buffer [50 mM citrate (pH 6.0), 0.1 M NaCl, 1 mM dithiothreitol (DTT), and 1 mM EDTA] with or without test compounds in triplicate.…”

Section: Methodsmentioning

confidence: 99%

Hydroxyoleoside-type seco-iridoids from Symplocos cochinchinensis and their insulin mimetic activity

Lee

Pham

et al. 2019

Sci Rep

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As part of an ongoing study of new insulin mimetic agents from medicinal plants, the 70% EtOH extract of Symplocos cochinchinensis was found to have a stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. The intensive targeted isolation of this active extract resulted in ten new hydroxyoleoside-type compounds conjugated with a phenolic acid and monoterpene (1–6 and 8–11), as well as four known compounds (7 and 12–14). The chemical structures of the new compounds were determined based on spectroscopic data analysis (1H and 13C NMR, HSQC, HMBC, NOESY and MS). The absolute configurations of the isolated compounds were determined by electronic circular dichroism (ECD) analysis of derivatives obtained after a series of reactions, such as those with dirhodium (ІІ) tetrakis (trifluoroacetate) and dimolybdenum (ІІ) tetraacetate. In vitro, compounds 3, 7 and 8 moderately increased the 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) uptake level in differentiated 3T3-L1 adipocytes. For further studies, we evaluated their effects on the expression of glucose transporter-4 (GLUT4), its translocation, protein tyrosine phosphatase 1B (PTP1B) inhibition and expression of phosphorylated Akt. Our results strongly suggest that the traditional uses of this plant can be described as active constituents by hydroxyoleoside-type compounds.

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PTP1B inhibitors from the seeds of Iris sanguinea and their insulin mimetic activities via AMPK and ACC phosphorylation

Cited by 26 publications

References 33 publications

Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway

Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway

Establishment of an efficient in vitro propagation system for Iris sanguinea

Hydroxyoleoside-type seco-iridoids from Symplocos cochinchinensis and their insulin mimetic activity

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