Screening of an annotated compound library for drug activity in a resistant myeloma cell line

Rickardson, Linda; Fryknäs, Mårten; Haglund, Caroline; Lövborg, Henrik; Nygren, Peter; Gustafsson, Mats; Isaksson, Anders; Larsson, Rolf

doi:10.1007/s00280-006-0216-7

Cited by 37 publications

(36 citation statements)

References 22 publications

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“…Only 0.2% of the compounds were identified as hits using 50% percent inhibition at 1 µg/ml as the cut-off criterion. This hit rate is clearly lower compared to that observed in cell lines [29]. This may be due to several factors.…”

Section: Discussioncontrasting

confidence: 59%

Phenotype-based drug screening in primary ovarian carcinoma cultures identifies intracellular iron depletion as a promising strategy for cancer treatment

Gullbo

Fryknäs

Rickardson

et al. 2011

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The results indicate the feasibility of using PCPTC for cancer drug screening and that intracellular iron depletion could be a potentially important strategy for cancer therapy.

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Section: Discussioncontrasting

confidence: 59%

Phenotype-based drug screening in primary ovarian carcinoma cultures identifies intracellular iron depletion as a promising strategy for cancer treatment

Gullbo

Fryknäs

Rickardson

et al. 2011

Biochemical Pharmacology

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“…STAT1 was one of the top genes whose expression positively correlated with resistance to doxorubicin and topoisomerase-II inhibitors (27). Upregulation of STAT1 in doxorubicin-resistant cell lines was accompanied by the upregulation of ISGs that overlapped, in part, with the IRDS genes (28). STAT1-dependent resistance to doxorubicin was associated with increased resistance to ionizing radiation (23).…”

Section: Chemoresistance and The Stat1 Pathwaymentioning

confidence: 99%

Molecular Pathways: Interferon/Stat1 Pathway: Role in the Tumor Resistance to Genotoxic Stress and Aggressive Growth

Khodarev

Roizman²,

Weichselbaum³

2012

Clinical Cancer Research

152

167

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STAT1 is activated by IFNs and other cell signals. Following activation, STAT1 is translocated to the nuclei and activates transcription of IFN-stimulated genes. Although the activation of STAT1 by IFNs is classically associated with antiviral defense and tumor-suppressive functions, emerging data indicate that expression of the STAT1 pathway confers cellular resistance to DNA-damaging agents and mediates aggressive tumor growth. Recent advances in the development of Janus-activated kinase/Stat inhibitors and peptide inhibitors specific for individual Stat proteins may provide new insights into the controversial functions of this pathway. Clin Cancer Res; 18(11); 3015-21. Ó2012 AACR.

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“…The effects of celecoxib in combination with cisplatin, doxorubicin, etoposide, irinotecan, or vincristine were investigated in SH-SY5Y and SK-N-BE(2) neuroblastoma cells. For this purpose, the previously described fluorometric microculture cytotoxicity assay was used (29,30). Briefly, 384-well microtiter plates (Nunclon surface, NUNC Brand Products, Roskilde, Denmark) were prepared with drug solutions in duplicate at 10 times the desired final drug concentration.…”

Section: Methodsmentioning

confidence: 99%

Celecoxib Prevents Neuroblastoma Tumor Development and Potentiates the Effect of Chemotherapeutic Drugs In vitro and In vivo

Ponthan

Wickström

Gleissman

et al. 2007

Clinical Cancer Research

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Purpose: Neuroblastoma is the most common and deadly solid tumor of childhood. Cyclooxygenase-2 is expressed in clinical neuroblastoma tumors and cell lines and inhibitors of this enzyme induce apoptosis in human neuroblastoma cells in vitro and in neuroblastoma xenografts in vivo. We hypothesized that the cyclooxygenase-2^specific inhibitor celecoxib could enhance the cytotoxic effect of chemotherapeutic drugs currently used in neuroblastoma treatment. Furthermore, we investigated if prophylactic treatment with celecoxib could prevent neuroblastoma tumor development in vivo. Experimental Design: Neuroblastoma cell cytotoxicity of chemotherapeutic drugs in combination with celecoxib was examined. In vivo, athymic rats carrying established SH-SY5Y xenografts were treated with celecoxib in combination with irinotecan, doxorubicin or etoposide, or with either drug alone. For prevention studies, rats received celecoxib in the diet, 250 to 2,500 ppm, from the time of tumor cell injection. Results: Celecoxib induced a synergistic or an additive cytotoxic effect in combination with doxorubicin, etoposide, irinotecan or vincristine in vitro. In vivo, treatment with celecoxib in combination with irinotecan or doxorubicin induced a significant growth inhibition of established neuroblastoma tumors. Rats receiving celecoxib in the diet showed a distinct dose-dependent delay in tumor development compared with untreated rats. Plasma levels of celecoxib were comparable with levels obtainable in humans. Conclusions: Celecoxib potentiates the antitumor effect of chemotherapeutic drugs currently used in neuroblastoma treatment, which argues for clinical trials combining these drugs. Celecoxib could also be a potential drug for treatment of minimal residual disease.

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Screening of an annotated compound library for drug activity in a resistant myeloma cell line

Abstract: In conclusion, screening of mechanistically annotated compounds on drug-resistant cancer cells can identify compounds with selective activity and provide a basis for the development of novel treatments of drug-resistant malignancies.

Cited by 37 publications

References 22 publications

Phenotype-based drug screening in primary ovarian carcinoma cultures identifies intracellular iron depletion as a promising strategy for cancer treatment

Phenotype-based drug screening in primary ovarian carcinoma cultures identifies intracellular iron depletion as a promising strategy for cancer treatment

Molecular Pathways: Interferon/Stat1 Pathway: Role in the Tumor Resistance to Genotoxic Stress and Aggressive Growth

Celecoxib Prevents Neuroblastoma Tumor Development and Potentiates the Effect of Chemotherapeutic Drugs In vitro and In vivo

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