Novel Survivin Inhibitor YM155 elicits Cytotoxicity in Glioblastoma Cell Lines with Normal or Deficiency DNA-Dependent Protein Kinase Activity

Lai, Pei Chun; Chen, Shu Huey; Yang, Sung-Byung; Cheng, Chuan; Chiu, Ted H.; Huang, Yuejiao

doi:10.1016/j.pedneo.2012.04.008

Cited by 17 publications

(14 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, survivin inhibitor YM155 promoted apoptosis of cancer cells (19,51), and we also observed that YM155 induced apoptosis in TCC cells with enhanced expression of cleaved PARP and phospho-histone γ-H2AX. PARP is involved in the repair of single-strand DNA nicks, but cleaved PARP facilitates cellular disassembly and promotes ongoing apoptosis (52).…”

Section: Discussionsupporting

confidence: 59%

See 1 more Smart Citation

Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

Abstract. Survivin is overexpressed in transitional cell carcinoma (TCC), the most common type of bladder cancer. Previous reports demonstrated that knockdown of survivin by siRNA induced apoptosis of TCC cells. The present study evaluated the therapeutic effects of sepantronium bromide (YM155), a novel small molecule survivin inhibitor under clinical trials, on TCC cells in vitro. BFTC905, a grade III TCC cell line derived from a patient of blackfoot disease in Taiwan, was the most gemcitabine-resistant cell line when compared to BFTC909, TSGH8301 and T24 in cytotoxicity assay, resulting from upregulation of securin and bcl-2 after gemcitabine treatment. YM155 caused potent concentration-dependent cytotoxicity in 4 TCC cell lines (IC 50 s ≤20 nM), but exhibited no cytotoxicity in survivin-null primary human urothelial cells. For BFTC905 cells, addition of gemcitabine and/or cisplatin, the standard TCC chemotherapy regimen, to YM155 did not exert additive cytotoxic effects. Molecular analyses indicated that YM155 inhibited the proliferation of BFTC905 cells by increasing p27 kip1 , suppressing Ki-67, and inducing quiescence. In addition, YM155 elicited apoptosis manifested with DNA fragmentation through suppressing the expression of survivin, securin and bcl-2. Furthermore, YM155 induced autophagy in BFTC905 cells as autophagic inhibitor, 3-methyladenine, attenuated YM155-induced LC3B-II levels and reversed the cytotoxicity of YM155. mTOR inhibitors sirolimus and everolimus did not increase YM155-induced expression of LC3B-II nor augment YM155-induced cytotoxicity. These results indicate that YM155 exerts its lethal effect on BFTC905 cells via apoptotic and autophagic death pathways and suggest that YM155 may be a potential drug for the therapy of gemcitabine-resistant bladder cancer.

show abstract

Section: Discussionsupporting

confidence: 59%

“…The Cell Death Detection ELISA plus (Roche, Mannheim, Germany) assay kit was used to differentiate apoptotic or necrotic condition of 2x10 4 BFTC905 cells after YM155 treatment. Procedures were followed as previously described (19 …”

Section: Methodsmentioning

confidence: 99%

Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…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: 87%

“…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

View full text Add to dashboard Cite

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.

show abstract

“…It also suppressed EGFR signaling, in part by inducing the proteasomal degradation of EGFR [23]. The levels of other cancer related molecules like PI3K, ERK, STAT3, securin were also diminished in the presence of YM155 [23,24]. A transcriptome analysis of Wilms' tumor cells treated with YM155 revealed down-regulation of several other genes besides survivin as well as the up-regulation of the pro-apoptotic genes caspase 9 and DIABLO [25].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study

Sim

Yee

et al. 2015

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Novel Survivin Inhibitor YM155 elicits Cytotoxicity in Glioblastoma Cell Lines with Normal or Deficiency DNA-Dependent Protein Kinase Activity

Cited by 17 publications

References 38 publications

Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells

Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells

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

Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study

Contact Info

Product

Resources

About