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

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.