Cedrol suppresses glioblastoma progression by triggering DNA damage and blocking nuclear translocation of the androgen receptor

Chang, Kai‐Fu; Huang, Xiao‐Fan; Chang, Jinghua Tsai; Huang, Ya‐Chih; Weng, Jun‐Cheng; Tsai, Nu‐Man

doi:10.1016/j.canlet.2020.09.007

Cited by 31 publications

(21 citation statements)

References 47 publications

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“…[ 29 ] Another recent study reported that cedrol (a sequesterine alcohol that has antimicrobial and anticancer properties) inhibited the growth of GBM cells and induced apoptosis (in synergy with TMZ) in vitro as well as in vivo in mouse models. [ 36 ] Interestingly, cedrol inhibited GBM via blocking AR; this was shown using bioinformatics analyses. [ 36 ] They also showed that cedrol blocked AR nuclear translocation, reduced cell viability, and mRNA expression of AR activated genes (like KLK3 and TMPRSS2) in DHT-treated cells compared to control.…”

Section: Role Of Androgens In Gliomamentioning

confidence: 99%

“…[ 36 ] Interestingly, cedrol inhibited GBM via blocking AR; this was shown using bioinformatics analyses. [ 36 ] They also showed that cedrol blocked AR nuclear translocation, reduced cell viability, and mRNA expression of AR activated genes (like KLK3 and TMPRSS2) in DHT-treated cells compared to control. [ 36 ] Overall, AR signaling seems to be pro-tumorigenic and AR antagonists have shown some efficacy in vitro and in vivo in animal models.…”

Section: Role Of Androgens In Gliomamentioning

confidence: 99%

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Insights into the role of estrogens and androgens in glial tumorigenesis

Daswani¹,

Khan²

2021

J Carcinog

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Gliomas are more common in males than in females. Emerging evidence from several studies in vitro and in vivo have shown the role of estrogens and androgens in glial tumorigenesis. In recent times, studies have also shed light on the actions of estrogen receptors, alpha and beta, and androgen receptor. Here, we provide a comprehensive overview of the research hitherto on estrogens and androgens along with an emphasis on their receptors in glioma pathophysiology. Studies with conflicting results are discussed and future possibilities are put forward. A collective understanding of the studies on these steroid hormones in glioma may serve to create an amalgamated therapeutic approach; and thereby, augment the efforts in tackling this deadly disease.

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Section: Role Of Androgens In Gliomamentioning

confidence: 99%

Section: Role Of Androgens In Gliomamentioning

confidence: 99%

Insights into the role of estrogens and androgens in glial tumorigenesis

Daswani¹,

Khan²

2021

J Carcinog

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“…CE, which holds rich biological actions, has been proved to be a functional composition in diversified plants. 34,46 In the present study, the ameliorated RA properties of CE were evaluated to justify its role in ginger. The analgesia and antiinflammatory effects are the basis for the RA study.…”

Section: ■ Discussionmentioning

confidence: 99%

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation

Zhang

Shen

Zhao³

et al. 2021

J. Agric. Food Chem.

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Ginger, as a food spice, is widely applied due to its extensive effects. Cedrol (CE) found in ginger is a sesquiterpene with anti-inflammatory activity. The objective of this research is to discuss the efficacy of CE on ameliorating rheumatoid arthritis (RA). CE inhibited chronic inflammation and pain in a dose-dependent manner accompanied by rapid onset and long duration. Besides, CE treatment effectively ameliorated the paw edema volume and arthritis score with no significant effect on body weight. Organ index, T-cell and B-cell proliferation, histopathology, and immunohistochemistry demonstrated that CE had immunological enhancement and attenuated RA effects. Remarkably, inhibition of phosphorylated-JAK3 protein, thereby abating the secretion of pro-inflammatory cytokines and inflammation-related mediators, was involved in the potential mechanism of CE efficiency through forming a hydrogen bond with ARG953 and ILE955 in the JAK3 active pocket. At the same time, the pharmacokinetic results showed that the absolute bioavailability of CE at 20, 40, and 80 mg/kg was 30.30, 23.68, and 16.11%, respectively. The current results offered clues for mastering the ameliorated RA of CE and further perfected the effective substance basis on the antiinflammatory effect of ginger, which was beneficial for further applications.

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“…Similarly, ZEB1 is a key regulator in epithelial-to-mesenchymal (proneural-to-mesenchymal) transition and associated chemoresistance mechanisms (25,26). AR signaling has been shown to be active in GBM cells in vitro and may relate to radiation resistance (27,28). Based on our analysis of integrated transcriptional and chromatin accessibility data, we conclude that these TFs likely play key roles in the regulation of tumor cell states in the primary tumor.…”

Section: Scsygnal Identifies a Network Of Regulators Mediating Treatmmentioning

confidence: 71%

A single-cell based precision medicine approach using glioblastoma patient-specific models

Park

Feroze

Emerson

et al. 2021

Preprint

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Glioblastoma (GBM) is a heterogeneous tumor made up of cell states that evolve over time. Here, we modeled tumor evolutionary trajectories during standard-of-care treatment using multimodal single-cell analysis of a primary tumor sample, corresponding mouse xenografts subjected to standard of care therapy, and recurrent tumor at autopsy. We mined the multimodal data with single cell SYstems Genetics Network AnaLysis (scSYGNAL) to identify a network of 52 regulators that mediate treatment-induced shifts in xenograft tumor-cell states that were also reflected in recurrence. By integrating scSYGNAL-derived regulatory network information with transcription factor accessibility deviations derived from single-cell ATAC-seq data, we developed consensus networks that regulate subpopulations of primary and recurrent tumor cells. Finally, by matching targeted therapies to active regulatory networks underlying tumor evolutionary trajectories, we provide a framework for applying single-cell-based precision medicine approaches in a concurrent, neo-adjuvant, or recurrent setting.SummaryInference of mechanistic drivers of therapy-induced evolution of glioblastoma at single cell resolution using RNA-seq and ATAC-seq from patient samples and model systems undergoing standard-of-care treatment informs strategy for identification of tumor evolutionary trajectories and possible cell state-directed therapeutics.

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Cedrol suppresses glioblastoma progression by triggering DNA damage and blocking nuclear translocation of the androgen receptor

Cited by 31 publications

References 47 publications

Insights into the role of estrogens and androgens in glial tumorigenesis

Insights into the role of estrogens and androgens in glial tumorigenesis

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation

A single-cell based precision medicine approach using glioblastoma patient-specific models

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