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Indirubin-3‘-Monoxime, an Inhibitor of Cyclin Dependent Kinases, Induces Growth Inhibition and Apoptosis in Renal Cell Cancer in vitro

Indirubin-3‘-Monoxime, an Inhibitor of Cyclin Dependent Kinases, Induces Growth Inhibition and... The compound indirubin is the active constituent of a traditionalChinese phytomedicine (Danggui Longhui Wan).This preparation has been used for years in the treatmentof chronic myelocytic leukemia. A derivate of the originalindirubin compound is indirubin-3'-monoxime which is aselective and potent inhibitor of cyclin-dependent kinases.In this study we investigated if indirubin-3'-monoximecan induce apoptosis and tumor cell death in 3 human(A498, CAKI-1, CAKI-2) and 1 murine (RENCA) renal cellcancer cell lines. The growth inhibitory and apoptosis inductionproperties were evaluated by EZ4U, a cytotoxicassay and by flow cytometry of annexin-V/PI stainingduring treatment with doses ranging from 5.0 to 15.0 µmindirubin-3'-monoxime over 72 h. To further evaluate theunderlying molecular actions of indirubin-3'-monoxime,survivin, a major antiaptotic protein, was additionallydetermined by intracellular flow cytometry. Our resultsshow that indirubin-3'-monoxime induces growth arrestand apoptosis in all RCC cell lines. All RCC lines expressedsurvivin. However, no clear correlation between apoptosisinduction and expression of survivin was found. As treatmentof metastatic RCC remains a challenge, the need for continuing assessment of novel agents in the treatment ofthis disease is mandatory. Indirubin-3'-monoxime seems acandidate for further evaluation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Urology Karger

Indirubin-3‘-Monoxime, an Inhibitor of Cyclin Dependent Kinases, Induces Growth Inhibition and Apoptosis in Renal Cell Cancer in vitro

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Publisher
Karger
Copyright
© 2007 S. Karger AG, Basel
ISSN
1661-7649
eISSN
1661-7657
DOI
10.1159/000106523
Publisher site
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Abstract

The compound indirubin is the active constituent of a traditionalChinese phytomedicine (Danggui Longhui Wan).This preparation has been used for years in the treatmentof chronic myelocytic leukemia. A derivate of the originalindirubin compound is indirubin-3'-monoxime which is aselective and potent inhibitor of cyclin-dependent kinases.In this study we investigated if indirubin-3'-monoximecan induce apoptosis and tumor cell death in 3 human(A498, CAKI-1, CAKI-2) and 1 murine (RENCA) renal cellcancer cell lines. The growth inhibitory and apoptosis inductionproperties were evaluated by EZ4U, a cytotoxicassay and by flow cytometry of annexin-V/PI stainingduring treatment with doses ranging from 5.0 to 15.0 µmindirubin-3'-monoxime over 72 h. To further evaluate theunderlying molecular actions of indirubin-3'-monoxime,survivin, a major antiaptotic protein, was additionallydetermined by intracellular flow cytometry. Our resultsshow that indirubin-3'-monoxime induces growth arrestand apoptosis in all RCC cell lines. All RCC lines expressedsurvivin. However, no clear correlation between apoptosisinduction and expression of survivin was found. As treatmentof metastatic RCC remains a challenge, the need for continuing assessment of novel agents in the treatment ofthis disease is mandatory. Indirubin-3'-monoxime seems acandidate for further evaluation.

Journal

Current Urology – Karger

Published: Jan 1, 2007

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