The Proapoptotic Effect of Formononetin in Human Osteosarcoma Cells: Involvement of Inactivation of ERK and Akt Pathways

Liu, Yun; He, Jinjie; Chen, Xiaoming; Li, Jian; Shen, MaoRong; Yu, Wen-Jun; Yang, Yixia; Xiao, Zengming

doi:10.1159/000363029

Cited by 36 publications

(35 citation statements)

References 33 publications

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“…Osteosarcoma (OS), the primary malignant bone tumor in young adults and children, is frequently derived from long bones and characterized by osteoid production produced by malignant cells (1)(2)(3)(4)(5). OS has high mobility and aggressivity, mainly to the lung.…”

Section: Introductionmentioning

confidence: 99%

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Shu¹,

Ye²,

Gu³

et al. 2018

BLL

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OBJECTIVE: This study aimed to investigate the exact role of miR-663b in osteosarcoma (OS) progression and further explore the underlying molecular mechanisms. MATERIALS AND METHODS: The miR-663b expression in human OS cell lines was determined by qRT-PCR, and the results suggested that miR-663b was highly expressed in human OS cells. TargetScan was used to predict the potential targets of miR-663b, and the prediction was confi rmed by dual-luciferase reporter assay. To investigate the role of miR-663b in OS, miR-663b was down-regulated in U2OS cells using miR-663b inhibitor. CCK8 and fl ow cytometry were preformed to investigate the proliferation and apoptosis of U2OS cells. Moreover, qRT-PCR and western blot analysis were performed to measure the mRNA and protein expression. RESULTS: We found that miR-663b directly targets TP73 and negatively regulates TP73 expression. MiR-663b inhibitor signifi cantly decreased the proliferation ability of U2OS cells, while the percentage of apoptotic cells was markedly increased. The level of Bcl-2 was notably inhibited by miR-663b inhibitor, while Bax expression was signifi cantly enhanced. Moreover, miR-663b down-regulation promoted p53 and p21 expression in U2OS cells. CONCLUSIONS: MiR-663b down-regulation represses proliferation and induces apoptosis in OS by targeting TP73. Therefore, we provide a potential therapeutic target for OS treatment (Fig. 6, Ref. 27). Text in PDF www.elis.sk.

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Section: Introductionmentioning

confidence: 99%

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Shu¹,

Ye²,

Gu³

et al. 2018

BLL

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“…Such as, allicin suppresses pancreatic cancer cell via apoptotic pathway, and curcumin plays a crucial role in anti-lung cancer activity. Moreover, it is reported that formononetin plays an important function on anti-cancer activity against osteosarcoma [7,8,9]. Osthole is one of effective monomers found in Cnidium monnieri .…”

Section: Introductionmentioning

confidence: 99%

Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

Wang

Lei

et al. 2016

Cell Physiol Biochem

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Background/Aims: Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear. Methods: Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG-63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot. Results: The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo. Conclusion: Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma.

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“…Li et al showed that formononetin inhibited the proliferation of human prostate cancer cells via inducing cell cycle arrest (8). Liu et al showed that formononetin suppressed proliferation while inducing the apoptosis of osteosarcoma cells (23). However, the effects of formononetin on VSMCs proliferation have been hitherto unclear.…”

Section: Discussionmentioning

confidence: 99%

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

Chen

Liu

Cai

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis.

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The Proapoptotic Effect of Formononetin in Human Osteosarcoma Cells: Involvement of Inactivation of ERK and Akt Pathways

Cited by 36 publications

References 33 publications

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

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