Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin

Li, Tao; Sheng, Xiaobo; Zhang, Lei; Li, Weidong; Wei, Zhonghong; Zhu, P.; Zhang, Feng; Wang, Aiyun; Woodgett, James R.; Lu, Yin

doi:10.1016/j.bcp.2016.06.009

Cited by 27 publications

(18 citation statements)

References 37 publications

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“…Previous studies showed that xanthatin had an antitumour effect in several tumour cells, including A549 nonsmall cell lung cancer cells, H1299 nonsmall cell lung cancer cells, B16‐F10 murine melanoma cells, human breast cancer MDA‐MB‐231 cells, HL‐60 cells, the human leukemic mast cell line LAD2, and Chinese hamster ovary cells (Li et al, ; Sanchez‐Lamar et al, ; Takeda, Nishimura, et al, ; Takeda, Noguchi, et al, ; Tao et al, ; Tao et al, ; Tao et al, ; Vera et al, ; Yu et al, ; L. Zhang, Ruan, et al, ). Here, we found that xanthatin significantly inhibited tumour growth in both nude mouse xenograft glioma and rat orthotopic implanted glioma in a dose‐dependent manner.…”

Section: Discussionmentioning

confidence: 99%

The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging

Wei

et al. 2018

Phytotherapy Research

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To investigate the suppressive effects of xanthatin on glioma growth in a nude mouse xenograft model and rat orthotopic implantation model using magnetic resonance imaging (MRI) to dynamically monitor the antitumour growth and antiangiogenesis effects of xanthatin. The nude mouse xenograft tumour model and rat orthotopic implantation model were established to observe the antitumour effects of xanthatin in vivo. In the rat orthotopic implanted tumour model, MRI scanning was used to dynamically monitor the antitumour growth effect and evaluate the antiangiogenesis effect of xanthatin. We found that xanthatin at a dose of 0.4 mg/10 g dramatically decreased the growth of xenograft tumours in nude mice. The antiangiogenesis effect of xanthatin C6 glioma was evaluated by dynamic contrast-enhanced (DCE) MRI via comparison of the volume transfer constant (K trans ) value, a parameter that reflects vessel permeability. We found that xanthatin at the doses of 8 and 16 mg/kg significantly decreased the K trans value, which suggests that xanthatin has antiangiogenesis effects. These data demonstrate the suppressive effects of xanthatin on C6 glioma occur via antiangiogenesis. Meanwhile, this study also provides evidence for the application of quantitative parameters of DCE-MRI for dynamically evaluating the growth and angiogenesis of intracranial tumours and for experimental and clinical research.

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Section: Discussionmentioning

confidence: 99%

The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging

Wei

et al. 2018

Phytotherapy Research

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“…Tao et al studied the inhibitory effect of xanthatin (1–40 μM), an active agent in X. strumarium , against lung cancer cells (Cell lines of A549, H1975, H1299, H1650 and HCC827) and its potential mechanisms [66,67]. It found that xanthatin could downregulate the STAT3, GSK3β and β-catenin, moreover, xanthatin could also trigger Chk1-mediated DNA damage and destabilize Cdc25C via lysosomal degradation [66,67,68]. In 1995, Ahn et al isolated three cytotoxic compounds from the leaves of X. strumarium , among them, xanthatin and 8-epi-xanthatin possessed obvious anti-tumor activity on A549 cells with IC 50 (half maximal inhibitory concentration) values of 1.3 and 1.1 μg/mL, respectively [17].…”

Section: Pharmacologymentioning

confidence: 99%

Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Xanthium strumarium L.: A Review

et al. 2019

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Xanthium strumarium L. (Asteraceae) is a common and well-known traditional Chinese herbal medicine usually named Cang-Er-Zi, and has been used for thousands of years in China. The purpose of this paper is to summarize the progress of modern research, and provide a systematic review on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics, and toxicology of the X. strumarium. Moreover, an in-depth discussion of some valuable issues and possible development for future research on this plant is also given. X. strumarium, as a traditional herbal medicine, has been extensively applied to treat many diseases, such as rhinitis, nasal sinusitis, headache, gastric ulcer, urticaria, rheumatism bacterial, fungal infections and arthritis. Up to now, more than 170 chemical constituents have been isolated and identified from X. strumarium, including sesquiterpenoids, phenylpropenoids, lignanoids, coumarins, steroids, glycosides, flavonoids, thiazides, anthraquinones, naphthoquinones and other compounds. Modern research shows that the extracts and compounds from X. strumarium possess wide-ranging pharmacological effects, including anti- allergic rhinitis (AR) effects, anti-tumor effects, anti-inflammatory and analgesic effects, insecticide and antiparasitic effects, antioxidant effects, antibacterial and antifungal effects, antidiabetic effects, antilipidemic effects and antiviral effects. However, further research should focus on investigating bioactive compounds and demonstrate the mechanism of its detoxification, and more reasonable quality control standards for X. strumarium should also be established.

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“…Previous studies demonstrated that xanthatin exhibits a wide variety of bioactivities, including anticancer [ 6 , 7 ], antiangiogenesis [ 8 – 10 ], antiviral [ 10 ], antiinflammatory [ 11 ], antifungal [ 12 , 13 ], antibacterial [ 14 ], antitrypanosome [ 11 ], and antileishmanial [ 13 ] activities. In addition, xanthatin was reported to suppress proliferation and induce apoptosis in a wide variety of cancer cell culture systems, including non-small cell lung cancer cells (A549 and H522 cells), MKN-45 human gastric carcinoma cells, MDA-MB-231 human breast cancer cells, B16-F10 murine melanoma cells, and L1210 mouse leukemia cells [ 9 , 10 , 15 – 23 ]. Recently, we dynamically monitored the antitumor growth effect of xanthatin in glioma-bearing mice using conventional magnetic resonance imaging (MRI) and dynamic contrast-enhanced MRI [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway

Cao

et al. 2019

Acta Pharmacol Sin

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Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L. , which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1–15 μM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg −1 ·d −1 , ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.

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Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin

Cited by 27 publications

References 37 publications

The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging

The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging

Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Xanthium strumarium L.: A Review

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway

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