Bisphosphonates regulate cell proliferation, apoptosis and pro-osteoclastic expression in MG-63 human osteosarcoma cells

Chang, Jun; Wang, Wei; Zhang, Hui; Hu, Yong; Yin, Zongsheng

doi:10.3892/ol.2012.723

Cited by 29 publications

(20 citation statements)

References 30 publications

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“…Actin reorganization [ 26 ], cell cycle progression [ 46 ], apoptosis [ 47 ], angiogenesis [ 48 ], DNA repair [ 49 , 50 ], NF-kB signaling [ 51 ] are elucidated pathways through which ZOL exerts its anticancer activity. Our analysis showed that miRNAs are possible molecular mediators of these effects.…”

Section: Resultsmentioning

confidence: 99%

Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?

et al. 2016

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Zoledronic acid (ZOL), belonging to third generation bisphosphonate family, is a potent inhibitor of osteoclast-mediated bone resorption, widely used to effectively prevent osteolysis in breast cancer patients who develop bone metastases. Low doses of ZOL have been shown to exhibit a direct anticancer role, by inhibiting cell adhesion, invasion, cytoskeleton remodelling and proliferation in MCF-7 breast cancer cells. In order to identify the molecular mechanisms and signaling pathways underlying the anticancer activity exerted by ZOL, we analyzed for the first time the microRNA expression profile in breast cancer cells. A large-scale microarray analysis of 377 miRNAs was performed on MCF7 cells treated with 10 μM ZOL for 24 h compared to untreated cells. Furthermore, the expression of specific ZOL-induced miRNAs was analyzed in MCF-7 and SkBr3 cells through Real-time PCR. Low-dose treatment with ZOL significantly altered expression of 54 miRNAs. Nine upregulated and twelve downregulated miRNAs have been identified after 24 h of treatment. Also, ZOL induced expression of 11 specific miRNAs and silenced expression of 22 miRNAs. MiRNA data analysis revealed the involvement of differentially expressed miRNAs in PI3K/Akt, MAPK, Wnt, TGF-β, Jak-STAT and mTOR signaling pathways, and regulation of actin cytoskeleton. Our results have been shown to be perfectly coherent with the recent findings reported in literature concerning changes in expression of some miRNAs involved in bone metastasis formation, progression, therapy resistance in breast cancer. In conclusion, this data supports the hypothesis that ZOL-induced modification of the miRNA expression profile contributes to the anticancer efficacy of this agent.

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Section: Resultsmentioning

confidence: 99%

Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?

et al. 2016

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“…Transmission electron microscopy (TEM). TEM analysis was performed as previously described (17). The chondrocytes were harvested, and fixed in 2.5% glutaraldehyde in phosphate buffer, post-fixed in 2% osmium tetroxide and embedded in Luveak-812 (Nacalai Tesque, Inc., Kyoto, Japan).…”

Section: Methodsmentioning

confidence: 99%

The dual role of autophagy in chondrocyte responses in the pathogenesis of articular cartilage degeneration in osteoarthritis

Chang

Wang

Zhang

et al. 2013

International Journal of Molecular Medicine

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The present study aimed to analyze the responses to autophagy in osteoarthritis (OA) and aging chondrocytes in order to elucidate the role of autophagy in the pathogenesis of OA. We used multiple assays to confirm that autophagic activity was downregulated in chondrocytes of aged articular cartilage. Surprisingly, we found that the expression of autophagy-related proteins was not decreased in the tissues of patients with OA. We also observed that rapamycin-induced autophagy prevented the accumulation of subdiploid cells in young chondrocytes, while it induced cell death by autophagy in OA chondrocytes. Our results demonstrate that autophagic activity decreases with aging, and may be responsible for the cytoprotective effects in young cartilage. However, we found that autophagic activity in patients with OA was higher than in the aging group, and reported autophagic cell death in OA chondrocytes. These results suggest that autophagy plays both a cytoprotective and death-promoting role in the pathogenesis of OA.

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“…In addition to its bone-protective effects, ZA can prevent tumor progression (27). ZA was reported to inhibit the prenylation of small GTP-binding proteins, such as Ras.…”

Section: Discussionmentioning

confidence: 99%

Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras-TAp73-G6PD axis in bladder cancer cells

Wang

Cao

et al. 2015

Molecular Medicine Reports

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Abstract. Zoledronic acid (ZA) is the current standard of care for the therapy of patients with bone metastasis or osteoporosis. ZA inhibits the prenylation of small guanosine-5'-triphosphate (GTP)-binding proteins, such as Ras, and thus inhibit Ras signaling. The present study demonstrated that ZA inhibited cell proliferation and the pentose phosphate pathway (PPP) in bladder cancer cells. In addition, the expression of glucose-6-phosphate dehydrogenase (G6PD, the rate-limiting enzyme of the PPP) was found to be inhibited by ZA. Furthermore, the stability of TAp73, which activates the expression G6PD was decreased in zoledronic acid treated cells. Decreased levels of Ras-GTP and phosphorylated-extracellular signal-regulated kinase 1/2 were also observed following treatment with ZA. This may be due to the fact that activated Ras was reported to stabilize TAp73 inducing its accumulation. The inhibition of Ras activity by PT inhibitor II also significantly reduced the levels of TAp73 and G6PD and the PPP flux. Moreover, knockdown of TAp73, attenuated the PPP flux and eliminated the affection of ZA on the PPP flux. In conclusion, it was proposed that ZA can inhibit stability of TAp73 and attenuate the PPP via blocking Ras signaling in bladder cancer cells.

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Bisphosphonates regulate cell proliferation, apoptosis and pro-osteoclastic expression in MG-63 human osteosarcoma cells

Cited by 29 publications

References 30 publications

Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?

Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?

The dual role of autophagy in chondrocyte responses in the pathogenesis of articular cartilage degeneration in osteoarthritis

Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras-TAp73-G6PD axis in bladder cancer cells

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