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. 2011 Nov-Dec;29(6):815-20.
doi: 10.1016/j.urolonc.2009.10.005. Epub 2009 Nov 27.

Antiproliferative and apoptosis inducing effects of indirubin-3'-monoxime in renal cell cancer cells

Frank G E Perabo  1 , Gregor Landwehrs, Christian Frössler, Doris H Schmidt, S C Mueller
Affiliations

Antiproliferative and apoptosis inducing effects of indirubin-3'-monoxime in renal cell cancer cells

Frank G E Perabo et al. Urol Oncol. 2011 Nov-Dec.

Abstract

Objectives: Indirubin-3'-monoxime, which is a selective and potent inhibitor of cyclin-dependent kinases (CDKs) has shown preclinical activity in several human cancer cells. This study investigated if indirubin-3'-monoxime can induce apoptosis and tumor cell death in 3 human (A498, CAKI-1, CAKI-2) and 1 murine renal cell cancer (RENCA) cell line.

Methods: The growth inhibitory and apoptosis induction properties were evaluated by EZ4U, a cytotoxic assay and by flow cytometry of annexin-V/PI staining during treatment with doses ranging from 5.0 to 15.0 μM indirubin-3'-monoxime over 72 hours. To further establish the underlying molecular targets of indirubin-3'-monoxime, survivin, a major anti-apoptotic protein was additionally determined by intracellular flow cytometry.

Results: Our results show that indirubin-3'-monoxime induces growth arrest and apoptosis in all renal cell cancer (RCC) cell lines. All RCC lines expressed survivin. However, a clear correlation between apoptosis induction and expression of survivin was not found.

Conclusions: As treatment of metastatic renal cell cancer (mRCC) remains a challenge, and the need for continuing assessment of novel agents in the treatment of this disease is mandatory. Indirubin-3'-monoxime seems to be a candidate for further evaluation.

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