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

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, CAM-I, CAKI-2) and I 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 mu M 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. (C) 2011 Elsevier Inc. All rights reserved.