Quercetin suppresses the proliferation and metastasis of metastatic osteosarcoma cells by inhibiting parathyroid hormone receptor 1

Li, Shenglong; Pei, Yi; Wang, Wei; Liu, Fei; Zheng, Ke; Zhang, Xiaojing

doi:10.1016/j.biopha.2019.108839

Cited by 45 publications

(38 citation statements)

References 26 publications

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“…This study suggested that the inhibition of proliferation, migration and invasion of OS cells that resulted from this treatment are correlated with inhibition of PTHR1 (149). Moreover, a recent evidence revealed that blocking of PTHR1 in human Saos-2 and U2OS cell lines by using of Quercetin, a flavonoid found in vegetables, fruits, and grains, reduced metastatic cell invasion, proliferation, migration, and adhesion (148). These findings suggest that PTHR1 could be a novel and promising therapeutic target for OS.…”

Section: Species Referencesmentioning

confidence: 62%

“…Overexpression of PTHR1 is linked with increased invasion and proliferation Cell line Human (105) Knockdown of PTHR1 stimulated tumor differentiation and decreased invasion and growth Tissue Mouse (99) Blocking of PTHR1 reduced metastatic cell invasion, proliferation, migration and adhesion Cell line Human (148) Patients with strongly staining for PTHR1 OS tumors had reduced survival times compare to those with weak immunostaining intensity OS tumors Tissue Dog (39) Decreased mRNA expression of PTHR1 inhibited proliferation, migration and invasion Cell line Human (149) the association between overexpression of PTHR1 and OS progression ( Table 2). Mutsaers et al (100) detected PTHR1 in primary and metastatic OS of osteoblastic and fibroblastic subtypes in vivo from two different types of transgenic mice.…”

Section: Species Referencesmentioning

confidence: 99%

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Roles of Parathyroid Hormone-Related Protein (PTHrP) and Its Receptor (PTHR1) in Normal and Tumor Tissues: Focus on Their Roles in Osteosarcoma

et al. 2021

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Osteosarcoma (OS) is the most common primary bone tumor and originates from bone forming mesenchymal cells and primarily affects children and adolescents. The 5-year survival rate for OS is 60 to 65%, with little improvement in prognosis during the last four decades. Studies have demonstrated the evolving roles of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation, bone remodeling, regulation of calcium transport from blood to milk, regulation of maternal calcium transport to the fetus and reabsorption of calcium in kidneys. These two molecules also play critical roles in the development, progression and metastasis of several tumors such as breast cancer, lung carcinoma, chondrosarcoma, squamous cell carcinoma, melanoma and OS. The protein expression of both PTHrP and PTHR1 have been demonstrated in OS, and their functions and proposed signaling pathways have been investigated yet their roles in OS have not been fully elucidated. This review aims to discuss the latest research with PTHrP and PTHR1 in OS tumorigenesis and possible mechanistic pathways.This review is dedicated to Professor Michael Day who died in May 2020 and was a very generous collaborator.

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Section: Species Referencesmentioning

confidence: 62%

Section: Species Referencesmentioning

confidence: 99%

Roles of Parathyroid Hormone-Related Protein (PTHrP) and Its Receptor (PTHR1) in Normal and Tumor Tissues: Focus on Their Roles in Osteosarcoma

et al. 2021

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“…evidence showed that quercetin exerted its anti-cancer effects by suppressing proliferation and metastasis, and inducing apoptosis and autophagy. [38][39][40][41] Chuang et al demonstrated that quercetin enhanced the anti-cancer activity of trichostatin A by upregulating the p300 protein in lung cancer. 42 Lu et al showed that quercetin inhibited the migration and invasion of HCCLM3 cells by downregulating the expression of p-AKT1, Matrix Metalloproteinase (MMP) MMP-2, and MMP-9.…”

Section: Discussionmentioning

confidence: 99%

<p>Network Pharmacology-Based Prediction and Verification of the Active Ingredients and Potential Targets of Zuojinwan for Treating Colorectal Cancer</p>

Huang

Zhang

et al. 2020

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Background: Zuojinwan (ZJW), a famous Chinese medicine formula, has been widely used to treat colorectal cancer (CRC). However, its bioactive compounds, potential targets, and molecular mechanism remain largely elusive. Aim: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation were employed to investigate bioactive compounds, potential targets, and molecular mechanism of ZJW against CRC. Materials and Methods: Bioactive compounds and potential targets of ZJW, as well as related genes of CRC, were acquired from public databases. Important ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the findings. Results: A total of 36 bioactive ingredients of ZJW and 163 gene targets of ZJW were identified. The network analysis revealed that quercetin, baicalein, wogonin, beta-sitosterol, and isorhamnetin may be candidate agents. The AKT1, JUN, CDKN1A, BCL2L1, and NCOA1 could become potential drug targets. The KEGG indicated that PI3K-AKT signaling pathway may play an important role in the effect of ZJW against CRC. Molecular docking suggested that quercetin, baicalein, and wogonin combined well with AKT1 and JUN. The in vitro experiment showed that quercetin, the most important ingredient of ZJW, could induce apoptosis of HCT116 cells through PI3K-Akt signaling pathway. This finding was congruent with the prediction obtained through the network pharmacology approach. Conclusion: This study comprehensively illuminated the active ingredients, potential targets, and molecular mechanism of ZJW against CRC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of traditional Chinese medicine (TCM) formula treating for disease.

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“…12 For instance, quercetin-3-methyl ether exerts an inhibitory effect on the development of esophageal cancer via targeting the AKT/mTOR/p70S6K and MAPK signaling pathways 29 ; quercetin impedes the proliferation of hepatoma cells and induces their apoptosis via repressing the JAK2/STAT3 signaling pathway 30 ; in osteosarcoma, quercetin inhibits the proliferation and metastasis of tumor cells via suppressing the expression of parathyroid hormone receptor 1. 31 Moreover, quercetin enhances the radiosensitivity of tumor cells via modulating the expression of ATM kinase. 16 Additionally, quercetin represses DNA double-strand break repair and enhances radiosensitivity of human ovarian cancer through the p53-dependent endoplasmic reticulum stress pathway.…”

Section: Discussionmentioning

confidence: 99%

Quercetin radiosensitizes non‐small cell lung cancer cells through the regulation of miR‐16‐5p/WEE1 axis

et al. 2020

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Background Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non‐small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated. Method Radiation‐resistant NSCLC cell lines were established. Quantitative real‐time PCR (qRT‐PCR) was used to detect the expression of miR‐16‐5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation‐resistant cells. After being treated with different concentrations of quercetin and different doses of X‐ray, cell proliferation and apoptosis were monitored by CCK‐8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR‐16‐5p and WEE1 was verified via a dual fluorescent reporter gene assay. Results The expression of miR‐16‐5p was down‐regulated in radiation‐resistant cells, while the expression of WEE1 was up‐regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose‐ and time‐dependent manner. Furthermore, quercetin treatment increased the expression of miR‐16‐5p and decreased the expression of WEE1. The function of quercetin was reversed by miR‐16‐5p inhibitors or the transfection of WEE1 overexpressing plasmids. Conclusion In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR‐16‐5p and WEE1.

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Quercetin suppresses the proliferation and metastasis of metastatic osteosarcoma cells by inhibiting parathyroid hormone receptor 1

Cited by 45 publications

References 26 publications

Roles of Parathyroid Hormone-Related Protein (PTHrP) and Its Receptor (PTHR1) in Normal and Tumor Tissues: Focus on Their Roles in Osteosarcoma

Roles of Parathyroid Hormone-Related Protein (PTHrP) and Its Receptor (PTHR1) in Normal and Tumor Tissues: Focus on Their Roles in Osteosarcoma

<p>Network Pharmacology-Based Prediction and Verification of the Active Ingredients and Potential Targets of Zuojinwan for Treating Colorectal Cancer</p>

Quercetin radiosensitizes non‐small cell lung cancer cells through the regulation of miR‐16‐5p/WEE1 axis

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