<i>β</i>-Elemene Selectively Inhibits the Proliferation of Glioma Stem-Like Cells Through the Downregulation of Notch1

Feng, Hai; Wang, Jing; Jiang, Hao; Mei, Xin; Zhao, Yi; Chen, Fu‐Rong; Qu, Yue; Sai, Ke; Guo, Cheng; Yang, Qun; Zhang, Zong Ping; Chen, Zhong Ping

doi:10.5966/sctm.2016-0009

Cited by 32 publications

(25 citation statements)

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“…Western blot analysis was performed using a standard protocol 36 . Briefly, equal amounts of protein (30 μg) were separated via SDS-PAGE and electro-transferred onto polyvinylidene difluoride membranes (EMD Millipore).…”

Section: Western Blot Analysismentioning

confidence: 99%

Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

Cai

Wang

et al. 2019

Cell Death Dis

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Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser 473 and Thr 308 and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.

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Section: Western Blot Analysismentioning

confidence: 99%

Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

Cai

Wang

et al. 2019

Cell Death Dis

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“…The in vivo animal work followed previously published protocol [18]. Four-week-old female BALB/C nude mice (Charles River Laboratories, Beijing, China) were raised in Sun Yat-sen University Cancer Center (SYS-UCC) animal facilities.…”

Section: Xenograft Transplantation In Vivomentioning

confidence: 99%

Skp2 modulates proliferation, senescence and tumorigenesis of glioma

Hong

et al. 2020

Cancer Cell Int

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Background: Gliomas represent the largest class of primary central nervous system neoplasms, many subtypes of which exhibit poor prognoses. Surgery followed by radiotherapy and chemotherapy has been used as a standard strategy but yielded unsatisfactory improvements in patient survival outcomes. The S-phase kinase protein 2 (Skp2), a critical component of the E3-ligase SCF complex, has been documented in tumorigenesis in various cancer types but its role in glioma has yet to be fully clarified. In this study, we investigated the function of Skp2 in the proliferation, stem cell maintenance, and drug sensitivity to temozolomide (TMZ) of glioma. Methods:To investigate the role of Skp2 in the prognosis of patients with glioma, we first analyzed data in databases TCGA and GTEx. To further clarify the effect of Skp2 on glioma cell proliferation, we suppressed its level in glioblastoma (GBM) cell lines through knockdown and small molecule inhibitors (lovastatin and SZL-P1-41). We then detected cell growth, colony formation, sphere formation, drug sensitivity, and in vivo tumor formation in xenograft mice model.Results: Skp2 mRNA level was higher in both low-grade glioma and GBM than normal brain tissues. The knockdown of Skp2 increased cell sensitivity to TMZ, decreased cell proliferation and tumorigenesis. In addition, Skp2 level was found increased upon stem cells enriching, while the knockdown of Skp2 led to reduced sphere numbers. Downregulation of Skp2 also induced senescence. Repurposing of lovastatin and novel compound SZL-P1-41 suppressed Skp2 effectively, and enhanced glioma cell sensitivity to TMZ in vitro and in vivo. Conclusion:Our data demonstrated that Skp2 modulated glioma cell proliferation in vitro and in vivo, stem cell maintenance, and cell sensitivity to TMZ, which indicated that Skp2 could be a potential target for long-term treatment.

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“…Research has found that β-elemene has direct antitumor effects, and its antitumor mechanisms include inducing apoptosis [10], arresting the cell cycle [11], inhibiting angiogenesis and cell migration [12], enhancing the immunogenicity of tumor cells [13], promoting erythrocyte immune function, and inhibiting cancer stem cell-like effects [14]. β-Elemene not only has direct antitumor effects but also reverses multidrug resistance by reducing mitochondrial membrane potential, activating the intracellular redox system, and inducing apoptosis of tumor cells [10,15].…”

Section: Introductionmentioning

confidence: 99%

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

Xie

Lei

et al. 2020

BioMed Research International

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Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.

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β-Elemene Selectively Inhibits the Proliferation of Glioma Stem-Like Cells Through the Downregulation of Notch1

Cited by 32 publications

References 50 publications

Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

Skp2 modulates proliferation, senescence and tumorigenesis of glioma

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

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