Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis

Cao, Liang; Qu, Dingding; Wang, Huan; Zhou, Sha; Jia, Chenming; Shi, Zixuan; Wang, Zongren; Zhang, Jiän; Ma, Jing

doi:10.3390/ijms17111928

Cited by 50 publications

(43 citation statements)

References 32 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite advances in standard therapy, including diagnostic methods and treatment strategies, the prognosis for patients with GBM remains poor, with an average survival time of 12–15 month after diagnosis [3-5]. Therefore, new anticancer agents for treating this disease are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway

Jin¹,

Nie²,

Zhou³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Gliomas result in the highest morbidity and mortality rates of intracranial primary central nervous system tumors because of their aggressive growth characteristics and high postoperative recurrence. They are characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior in patients. Proliferation is a key aspect of the clinical progression of malignant gliomas, complicating complete surgical resection and enabling tumor regrowth and further proliferation of the surviving tumor cells. Methods: The expression of Fstl1 was detected by western blotting and qRT-PCR. We used cell proliferation and colony formation assays to measure proliferation. Then, flow cytometry was used to analyze cell cycle progression. The expression of Fstl1, p-Smad1/5/8 and p21 in GBM tissue sections was evaluated using immunohistochemical staining. Furthermore, we used coimmunoprecipitation (Co-IP) and immunoprecipitation to validate the relationship between Fstl1, BMP4 and BMPR2. Finally, we used orthotopic xenograft studies to measure the growth of tumors in vivo. Results: We found that follistatin-like 1 (Fstl1) was upregulated in high-grade glioma specimens and that its levels correlated with poor prognosis. Fstl1 upregulation increased cell proliferation, colony formation and cell cycle progression, while its knockdown inhibited these processes. Moreover, Fstl1 interacted with bone morphogenetic protein (BMP) 4, but not BMP receptor (BMPR) 2, and competitively inhibited their association. Furthermore, Fstl1 overexpression suppressed the activation of the BMP4/Smad1/5/8 signaling pathway, while BMP4 overexpression reversed this effect. Conclusion: Our study demonstrated that Fstl1 promoted glioma growth through the BMP4/Smad1/5/8 signaling pathway, and these findings suggest potential new glioblastoma treatment strategies.

show abstract

Section: Introductionmentioning

confidence: 99%

Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway

Jin¹,

Nie²,

Zhou³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Though used as a pesticide, recent studies have shown its anti-proliferative effect against lymphoma, leukemia and hepatocellular cancer cell lines [ 225 – 228 ]. In addition, TSN also inhibits proliferation of U87 and C6 cell line at nanomolar (10 nM) concentrations [ 229 ]. Additionally, TSN reduced the growth of U87 xenografts in vivo feasibly by upregulation of p53 and estrogen receptor β, which are known tumor suppressors in many cancers [ 229 – 231 ].…”

Section: Effects Of Natural Products On Gbm Pre-clinical Modelsmentioning

confidence: 99%

“…In addition, TSN also inhibits proliferation of U87 and C6 cell line at nanomolar (10 nM) concentrations [ 229 ]. Additionally, TSN reduced the growth of U87 xenografts in vivo feasibly by upregulation of p53 and estrogen receptor β, which are known tumor suppressors in many cancers [ 229 – 231 ].…”

Section: Effects Of Natural Products On Gbm Pre-clinical Modelsmentioning

confidence: 99%

Natural products: a hope for glioblastoma patients

et al. 2018

View full text Add to dashboard Cite

Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB). Cancer stem cells (CSCs) have intrinsic resistance to initial chemoradiation therapy (CRT) and acquire further resistance via deregulation of many signaling pathways. Due to the failure of classical chemotherapies and targeted drugs, research efforts focusing on the use of less toxic agents have increased. Interestingly, multiple natural compounds have shown antitumor and apoptotic effects in TMZ resistant and p53 mutant GBM cell lines and also displayed synergistic effects with TMZ. In this review, we have summarized the current literature on natural products or product analogs used to modulate the BBB permeability, induce cell death, eradicate CSCs and sensitize GBM to CRT.

show abstract

“…In addition, salicylketoxime-based ERβ agonists have also been found to reduce glioma growth in subcutaneous models [ 11 ]. Furthermore, the new potential ERβ agonist toosendanin (TSN) has also been shown to reduce tumor burden in a xenograft model of athymic nude mice [ 52 ]. However, these studies are limited by the lack of drug testing using an orthotopic model, and furthermore, when testing the efficacy of glioma chemotherapy drugs, the tumor microenvironment and the presence of a complete immune system must be considered.…”

Section: Various Erβ Agonists Could Exert Anti-glioma Activitiesmentioning

confidence: 99%

Update on the therapeutic significance of estrogen receptor beta in malignant gliomas

et al. 2017

View full text Add to dashboard Cite

Malignant glioma is the most fatal of the astrocytic lineage tumors despite therapeutic advances. Men have a higher glioma incidence than women, indicating that estrogen level differences between men and women may influence glioma pathogenesis. However, the mechanism underlying the anticancer effects of estrogen has not been fully clarified and is complicated by the presence of several distinct estrogen receptor types and the identification of a growing number of estrogen receptor splice variants. Specifically, it is generally accepted that estrogen receptor alpha (ERα) functions as a tumor promoter, while estrogen receptor beta (ERβ) functions as a tumor suppressor, and the role and therapeutic significance of ERβ signaling in gliomas remains elusive. Thus, a deeper analysis of ERβ could elucidate the role of estrogens in gender-related cancer incidence. ERβ has been found to be involved in complex interactions with malignant gliomas. In addition, the prognostic value of ERβ expression in glioma patients should not be ignored when considering translating experimental findings to clinical practice. More importantly, several potential drugs consisting of selective ERβ agonists have exhibited anti-glioma activities and could further extend the therapeutic potential of ERβ-selective agonists. Here, we review the literature to clarify the anti-glioma effect of ERβ. To clarify ERβ-mediated treatment effects in malignant gliomas, this review focuses on the potential mechanisms mediated by ERβ in the intracellular signaling events in glioma cells, the prognostic value of ERβ expression in glioma patients, and various ERβ agonists that could be potential drugs with anti-glioma activities.

show abstract

Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis

Cited by 50 publications

References 32 publications

Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway

Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway

Natural products: a hope for glioblastoma patients

Update on the therapeutic significance of estrogen receptor beta in malignant gliomas

Contact Info

Product

Resources

About