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

Huang, Yuejiao; Cheng, Chuan; Lin, Tzu; Chiu, Ted H.; Lai, Pei Chun

doi:10.3892/or.2013.2882

Cited by 11 publications

(14 citation statements)

References 51 publications

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“…Therefore the authors applied YM155, a survivin suppressant that is currently in clinical development and which inhibited the growth of 119 human cancer cell lines . Recently, a variety of publications have reported the down‐regulation of survivin and the close connection to apoptosis by YM155 . In the present study, YM155 led to a significant decrease of cell proliferation and furthermore apoptosis by Annexin was detected in a dose‐ and time‐dependent manner.…”

Section: Discussionsupporting

confidence: 48%

Examination of survivin expression in 50 chordoma specimens—A histological and in vitro study

Froehlich

Rinner

Deutsch

et al. 2015

Journal Orthopaedic Research

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Chordomas mainly arise along the axial skeleton and are characterized by their slow but destructive growth. Prognosis and quality of life are poor because treatment options are mainly limited to surgery and radiotherapy. Survivin, a member of the apoptosis inhibitor protein family, functions as a key regulator of mitosis and programmed cell death, and is overexpressed in many tumor types. The aim of this study was to determine the role of survivin in chordomas. Survivin expression was investigated in 50 chordoma samples and three chordoma cell lines using immunohistochemistry. The intensity of immunostaining was evaluated in regard to the development of recurrences. The immunohistochemical results were correlated with clinical parameters like gender, age, tumor size, and location and were performed in primary chordomas as well as in recurrent lesions. Furthermore, survivin knockdown experiments on chordoma cell lines were performed. YM155 decreased the growth behavior of chordoma cells dose-and time dependently. Transient knockdown of survivin led to a G2/M arrest, decreased proliferation, consistently induced an increase of polyploidy and morphological changes, and induced apoptosis. The resultant data from this study suggest that survivin plays a cell cycle-progressive role in chordomas. Hence, regulation of survivin by YM155 is a promising new target for the development of new therapeutic drugs. ß

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Section: Discussionsupporting

confidence: 48%

Examination of survivin expression in 50 chordoma specimens—A histological and in vitro study

Froehlich

Rinner

Deutsch

et al. 2015

Journal Orthopaedic Research

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“…Compensatory increase in the expression of anti-apoptotic protein Bcl-xL was found in our experiment, but overexpression of Bcl-xL was not correlated with the recurrence and survival of bladder cancer patients (60). In our previous study, upregulation of securin and Bcl-2 in BFTC905 cells may be a compensatory mechanism for gemcitabine resistance (22). Downregulated expression of securin, but no changes of Bcl-2 expression were observed after thalidomide treatment.…”

Section: Discussioncontrasting

confidence: 49%

“…Cells were maintained as described previously (20,21). BFTC905 cells were gemcitabine-resistant (22). We also used primary human urothelial cells (HUCs) (ScienCell Research Laboratories, Carlsbad, CA, USA) (22).…”

Section: Methodsmentioning

confidence: 99%

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Therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer

Huang¹,

Cheng²,

Chiu³

et al. 2015

International Journal of Oncology

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Controversial effects of thalidomide for solid malignancies have been reported. In the present study, we evaluate the effects of thalidomide for transitional cell carcinoma (TCC), the most common type of bladder cancer. Thalidomide precipitates were observed when its DMSO solution was added to the culture medium. No precipitation was found when thalidomide was dissolved in 45% γ-cyclodextrin, and this concentration of γ-cyclodextrin elicited slight cytotoxicity on TCC BFTC905 and primary human urothelial cells. Thalidomide-γ-cyclodextrin complex exerted a concentration-dependent cytotoxicity in TCC cells, but was relatively less cytotoxic (with IC50 of 200 µM) in BFTC905 cells than the other 3 TCC cell lines, possibly due to upregulation of Bcl-xL and HIF-1α mediated carbonic anhydrase IX, and promotion of quiescence. Gemcitabine-resistant BFTC905 cells were chosen for additional experiments. Thalidomide induced apoptosis through downregulation of survivin and securin. The secretion of VEGF and TNF-α was ameliorated by thalidomide, but they did not affect cell proliferation. Immune-modulating lenalidomide and pomalidomide did not elicit cytotoxicity. In addition, cereblon did not play a role in the thalidomide effect. Oxidative DNA damage was triggered by thalidomide, and anti-oxidants reversed the effect. Thalidomide also inhibited TNF-α induced invasion through inhibition of NF-κB, and downregulation of effectors, ICAM-1 and MMP-9. Thalidomide inhibited the growth of BFTC905 xenograft tumors in SCID mice via induction of DNA damage and suppression of angiogenesis. Higher average body weight, indicating less chachexia, was observed in thalidomide treated group. Sedative effect was observed within one-week of treatment. These pre-clinical results suggest therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer.

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“…Hypoxia also results in the accumulation of lactate dehydrogenase-A, which assists in the maintenance of the hypoxic phenotype and increasing chemoresistance (11). Novel molecular targets and molecules that have been identified include: Protein tyrosine kinase-6 (12); vitamin D receptor (VDR) (13); mucin-1 (MUC1) (14); ormeloxifene that targets the sonic hedgehog pathway (15); sodium metaarsenite (KML001) that targets the epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP) 2 (16); the quinazolinedione-based redox modulator QD232 that targets proto-oncogene tyrosine-protein kinase/focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 phosphorylation (17); aspirin, which was revealed to reduce tumor growth and sensitize cells to gemcitabine (18); the curaxin CBL0137, which targets NF-κB and ribonucleotide reductase (19) and sepantronium bromide (YM155) (20)(21)(22), which inhibits the action of inhibitor of apoptosis protein family members (20), as summarized in Table I.…”

Section: Gemcitabine Resistance Mechanismsmentioning

confidence: 99%

Chemoresistance in pancreatic cancer: Emerging concepts

Gnanamony

Gondi

2017

Oncology Letters

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Abstract. Pancreatic cancer is one of the most lethal types of cancer in the world. The incidence of pancreatic cancer increases each year with no significant decrease in mortality. Pancreatic cancer is a complex disease, and this complexity is partly attributed to late diagnosis, an aggressive phenotype, environmental factors and lack of effective treatment options. Surgical resection followed by adjuvant chemotherapy is the treatment of choice for early stage cancer, whereas gemcitabine is the standard first line therapy for patients with advanced stage disease. Treatment regimens comprising folinic acid, 5-fluorouracil, irinotecan, oxaliplatin and nab-paclitaxel have demonstrated modest effects in improving median survival rates. A number of other chemotherapeutics are currently undergoing clinical trials as components of combination therapies with gemcitabine. An increasing number of novel molecular targets and cellular pathways are being identified, which highlights the complexity of this disease. The development of chemoresistance to gemcitabine is multifactorial and there exists an interplay between pancreatic cancer cells, the tumor microenvironment and cancer stem cells. These components appear to be governed by a complex network of non-coding RNAs such as micro RNAs and long non-coding RNAs. In the present study, studies describing previous research on the understanding of the factors associated with the development of chemoresistance to gemcitabine in pancreatic cancer are reviewed. A comprehensive understanding of the multiple pathways of chemoresistance is key to develop next generation therapeutics to pancreatic cancer.

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

Cited by 11 publications

References 51 publications

Examination of survivin expression in 50 chordoma specimens—A histological and in vitro study

Examination of survivin expression in 50 chordoma specimens—A histological and in vitro study

Therapeutic potential of thalidomide for gemcitabine-resistant bladder cancer

Chemoresistance in pancreatic cancer: Emerging concepts

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