In vitro and in vivo Study on Glioma Treatment Enhancement by Combining Temozolomide with Calycosin and Formononetin

Ni, Qi; Fan, Yani; Zhang, Xiong; Fan, Hongwei; Li, Yingbin

doi:10.1016/j.jep.2019.01.023

Cited by 26 publications

(14 citation statements)

References 23 publications

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“…Studies have shown that the pharmacological properties of calycosin are probably related to its interaction with the estrogen receptors on the cell membrane and regulate TLR4/NF‐κB and MAPK pathways (Quan et al, 2015; Tang et al, 2010). Ni et al reported that 40 mg/kg calycosin were not toxic to heart, liver, spleen, lung, and kidney in mice (Ni, Fan, Zhang, Fan, & Li, 2019). Accordingly, in this study, we investigated the effect of calycosin in GC‐induced ONFH.…”

Section: Discussionmentioning

confidence: 99%

Calycosin modulates inflammation via suppressing TLR4/NF‐κB pathway and promotes bone formation to ameliorate glucocorticoid‐induced osteonecrosis of the femoral head in rat

Zhu

Liu

et al. 2021

Phytotherapy Research

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Section: Discussionmentioning

confidence: 99%

Calycosin modulates inflammation via suppressing TLR4/NF‐κB pathway and promotes bone formation to ameliorate glucocorticoid‐induced osteonecrosis of the femoral head in rat

Zhu

Liu

et al. 2021

Phytotherapy Research

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“…In C6 cells, formononetin enhances TMZ’s pro-apoptotic and anti-migratory effects by upregulating Bax and cleaved caspases and downregulating MMPs, respectively [ 39 , 40 ]. Similarly, formononetin and calycosin together potently increase the effectiveness of TMZ in C6 cells and a murine C6 xenograft model [ 40 ].…”

Section: Mechanisms Of Gbm and Synergistic Flavonoid-chemotherapeutic Effectsmentioning

confidence: 99%

Flavonoids Synergistically Enhance the Anti-Glioblastoma Effects of Chemotherapeutic Drugs

et al. 2021

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Flavonoids are polyphenolic plant secondary metabolites with pleiotropic biological properties, including anti-cancer activities. These natural compounds have potential utility in glioblastoma (GBM), a malignant central nervous system tumor derived from astrocytes. Conventional GBM treatment modalities such as chemotherapy, radiation therapy, and surgical tumor resection are beneficial but limited by extensive tumor invasion and drug/radiation resistance. Therefore, dietary flavonoids—with demonstrated anti-GBM properties in preclinical research—are potential alternative therapies. This review explores the synergistic enhancement of the anti-GBM effects of conventional chemotherapeutic drugs by flavonoids. Primary studies published between 2011 and 2021 on flavonoid–chemotherapeutic synergy in GBM were obtained from PubMed. These studies demonstrate that flavonoids such as chrysin, epigallocatechin-3-gallate (EGCG), formononetin, hispidulin, icariin, quercetin, rutin, and silibinin synergistically enhance the effects of canonical chemotherapeutics. These beneficial effects are mediated by the modulation of intracellular signaling mechanisms related to apoptosis, proliferation, autophagy, motility, and chemoresistance. In this light, flavonoids hold promise in improving current therapeutic strategies and ultimately overcoming GBM drug resistance. However, despite positive preclinical results, further investigations are necessary before the commencement of clinical trials. Key considerations include the bioavailability, blood–brain barrier (BBB) permeability, and safety of flavonoids; optimal dosages of flavonoids and chemotherapeutics; drug delivery platforms; and the potential for adverse interactions.

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“…A previous study by our group found that CA exerted anti-GBM effects by downregulating TGFβ and c-Met [10,11]. Furthermore, Ni Q et al reported that the combination of CA and temozolomide enhanced anti-tumor effects in GBM [24]. However, the underlying molecular target of CA in GBM remains to be completely investigated.…”

Section: Discussionmentioning

confidence: 95%

Calycosin(CA) Inhibits Proliferation, Migration and Invasion by Suppression of CXCL10 Signaling Pathway in Glioma

wang

Chen

et al. 2021

Preprint

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Background: Glioblastoma is a frequently encountered central nervous system malignancy. Calycosin, a bioactive compound extracted from dried Radix astragali root has exhibited anticancer activity across several different types of cancers, including glioma, but the therapeutic mode of action has yet to be clarified. One ubiquitous inflammatory chemokine implicated in cancer biology is the C-X-C chemokine ligand 10 (CXCL10). The current study seeks to investigate CXCL10 as a likely calycosin target in aiding its inhibitory effects on glioblastoma progression.Method: The clinical significance of CXCL10 including pathologic grade and survival rate in GBM patients were accessed from TCGA database and our clinical samples. CCK-8 experiments and clone formation assay were performed to detect the cell proliferation. Transwell assay was conducted to examined cell migration and invasion. Western blotting and immunofluorescence staining was used to analyze protein expression levels. Xenograft mouse model was used to evaluate the effect of CA in vivo. Results: Firstly, we demonstrated that CXCL10 expression is positively associated with glioma and correlated negatively to patient prognosis, supporting our hypothesis that CXCL10 was a potential target for GBM treatment. Additionally, U251 and U87 glioma cell lines were found to demonstrate inhibited invasive, migratory and proliferative abilities upon exposure to calycosin. Calycosin was then found to downregulate CXCL10 expression in a manner that increased with increasing doses, resulting in reduced downstream inflammatory cytokines including NLRP3, NF-κB, IL-1β. Moreover, we demonstrated that overexpressing CXCL10 abolished the inhibitory impact of calycosin on cellular invasion, migration and proliferation in glioma cell lines. Meanwhile, CXCL10 knockdown enhanced calycosin effects on GBM cells. We also used in vivo xenograft mice models to determine the impact of calycosin on glioma growth and obtained results similar to our in vitro experiments.Conclusions: The current investigation underscores the role of CXCL10 as a promising therapeutic target for treating GBM, with calycosin functioning as a future treatment modality.

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In vitro and in vivo Study on Glioma Treatment Enhancement by Combining Temozolomide with Calycosin and Formononetin

Cited by 26 publications

References 23 publications

Calycosin modulates inflammation via suppressing TLR4/NF‐κB pathway and promotes bone formation to ameliorate glucocorticoid‐induced osteonecrosis of the femoral head in rat

Calycosin modulates inflammation via suppressing TLR4/NF‐κB pathway and promotes bone formation to ameliorate glucocorticoid‐induced osteonecrosis of the femoral head in rat

Flavonoids Synergistically Enhance the Anti-Glioblastoma Effects of Chemotherapeutic Drugs

Calycosin(CA) Inhibits Proliferation, Migration and Invasion by Suppression of CXCL10 Signaling Pathway in Glioma

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