Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells

Tao, Yan-Fang; Lu, Jun; Du, Xiaohong; Sun, Lichao; Zhao, Xuan; Peng, Liang; Cao, Liu; Xiao, Pei-Fang; Pang, Li; Wu, Dong; Wang, Na; Feng, Xing; Li, Yanhong; Ni, Jian; Wang, Jian; Pan, Jian

doi:10.1186/1471-2407-12-619

Cited by 47 publications

(54 citation statements)

References 44 publications

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“…The results demonstrated that silencing of survivin expression, via specific inhibitor YM155, induced HCC cell apoptosis and growth arrest. These results corroborated those of previous studies regarding other neoplasms (8)(9)(10)(11)13,16). In order to represent a potential therapeutic strategy for HCC, the impacts of survivin, as well as YM155, on HCC should be sufficiently understood and validated.…”

Section: Discussionsupporting

confidence: 79%

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Silencing of survivin by YM155 induces apoptosis and growth arrest in hepatocellular carcinoma cells

et al. 2015

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Abstract. Survivin overactivation is a frequent event in human hepatocellular carcinoma (HCC), due to its function in the induction of hepatocyte proliferation and apoptotic dysfunction. Recently, a novel survivin inhibitor named YM155, has demonstrated broad antitumor effects against various malignant tumors. Therefore, the present study aimed to explore how this agent may impact on HCC and elucidate its underlying mechanism of action. Immunohistochemical analysis was performed on 8 specimens of human HCC, to assess the protein expression of survivin and phosphorylated retinoblastoma tumor suppressor (p-Rb). In addition, in vitro, HepG2 and Huh7 human HCC cell lines were exposed to 100 µM YM155 for up to 72 h and the cell viability was subsequently determined using MTT assay. Furthermore, the apoptotic status of YM155-treated HCC cells was investigated by flow cytometry, and the protein levels of survivin, procaspase-3 and p-Rb in YM155-treated HCC cells were assessed by immunoblotting analysis. The results demonstrated that HCC specimens expressed high levels of survivin and p-Rb protein compared with those of adjacent noncancerous liver tissues. In vitro, YM155 significantly induced HCC cell apoptosis and growth arrest. At the protein level, YM155 markedly inhibited survivin and p-Rb expression, and elevated procaspase-3. YM155 demonstrated significant antitumor effects on HCC cells in the present study. These effects were associated with its anti-proliferative and apoptosis-induction activities. YM155 requires further investigation as a novel agent for potential use as a therapeutic strategy for the treatment of HCC.

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Section: Discussionsupporting

confidence: 79%

“…To date, this novel, small, imidazolium-based chemical has exhibited broad antitumor effects on various tumors, including Wilm's tumor, glioblastoma and breast cancer (6)(7)(8)(9). In addition, ongoing studies have demonstrated that YM155 may also enhance the chemosensitivity of cells to existing anticancer agents (4,10,11).…”

Section: Introductionmentioning

confidence: 99%

Silencing of survivin by YM155 induces apoptosis and growth arrest in hepatocellular carcinoma cells

et al. 2015

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“…YM155 was identified in a high-throughput screen to identify agents that selectively block survivin promoter activity and is the most clinically advanced of this new class of agents (40). It has demonstrated activity against various tumor types in preclinical studies (19,(40)(41)(42)(43). We selected the VHL null 786-O and the VHL wild-type Caki-1 cell lines as models for our xenograft studies as they both displayed high basal survivin expression.…”

Section: Discussionmentioning

confidence: 99%

Targeting Survivin Inhibits Renal Cell Carcinoma Progression and Enhances the Activity of Temsirolimus

Carew

Espitia

Zhao

et al. 2015

Molecular Cancer Therapeutics

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Elevated expression of the antiapoptotic factor survivin has been implicated in cancer cell survival and disease progression. However, its specific contribution to renal cell carcinoma (RCC) pathogenesis is not well defined. We investigated the roles of survivin in RCC tumor progression, resistance to mTOR inhibitors, and evaluated the therapeutic activity of the survivin suppressant YM155 in RCC models. Here, we report that survivin expression levels were significantly higher in RCC cell lines compared with normal renal cells. Stable targeted knockdown of survivin completely abrogated the ability of 786-O RCC tumors to grow in mice, thus demonstrating its importance as a regulator of RCC tumorigenesis. We next explored multiple strategies to therapeutically inhibit survivin function in RCC. Treatment with the mTOR inhibitor temsirolimus partially diminished survivin levels and this effect was augmented by the addition of YM155. Further analyses revealed that, in accordance with their combined anti-survivin effects, YM155 significantly improved the anticancer activity of temsirolimus in a panel of RCC cell lines in vitro and in xenograft models in vivo. Similar to pharmacologic inhibition of survivin, shRNA-mediated silencing of survivin expression not only inhibited RCC tumor growth, but also significantly sensitized RCC cells to temsirolimus therapy. Subsequent experiments demonstrated that the effectiveness of this dual survivin/mTOR inhibition strategy was mediated by a potent decrease in survivin levels and corresponding induction of apoptosis. Our findings establish survivin inhibition as a novel approach to improve RCC therapy that warrants further investigation.

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“…Inhibition of TNFα and TNFR1 by a pharmacological inhibitor and genetic silencing, respectively, reduced SMAC mimetic/ IFNα-triggered apoptosis. Tao et al suggested that survivin, an inhibitor of apoptosis, inhibitor induced programmed cell death in Wilms tumor cells by increasing expression of TNFR1 signaling [126].…”

Section: Tnf and Tnf Receptor 1-2 (Tnfr1 And Tnfr2)mentioning

confidence: 99%

Major apoptotic mechanisms and genes involved in apoptosis

et al. 2016

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As much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues, organs and the whole organism. Apoptosis, a type of cell death mechanism, is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body. Apoptosis can be triggered by intrinsically or extrinsically through death signals from the outside of the cell. Any abnormality in apoptosis process can cause various types of diseases from cancer to auto-immune diseases. Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. In this review, we discuss the basic features of apoptosis and have focused on the gene families playing critical roles, activation/inactivation mechanisms, upstream/downstream effectors, and signaling pathways in apoptosis on the basis of cancer studies. In addition, novel apoptotic players such as miRNAs and sphingolipid family members in various kind of cancer are discussed.

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Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells

Cited by 47 publications

References 44 publications

Silencing of survivin by YM155 induces apoptosis and growth arrest in hepatocellular carcinoma cells

Silencing of survivin by YM155 induces apoptosis and growth arrest in hepatocellular carcinoma cells

Targeting Survivin Inhibits Renal Cell Carcinoma Progression and Enhances the Activity of Temsirolimus

Major apoptotic mechanisms and genes involved in apoptosis

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