Antiproliferative and apoptosis inducing effects of indirubin-3'-monoxime in renal cell cancer cells.
OBJECTIVE
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.
Perabo
Frank G E
FG
Department of Urology, University Hospital Bonn, Bonn, Germany. perabo@lycos.com
Landwehrs
Gregor
G
Frössler
Christian
C
Schmidt
Doris H
DH
Mueller
S C
SC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000378:metabolism*; D051379:Mice; D010091:Oximes / Q000494:pharmacology*; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D007211:Indoles; D051034:Inhibitor of Apoptosis Proteins; D010091:Oximes; D000077022:Survivin; C474021:indirubin-3'-monoxime