Seliciclib (CYC202; r-roscovitine) in combination with cytotoxic agents in human uterine sarcoma cell lines.
BACKGROUND
Inhibition of cyclin-dependent kinases (CDKs) has recently emerged as an interesting approach to treat human malignancies. This was explored in human leiomyosarcoma (LMS) lines, which represent a tumour associated with poor survival, chemo-unresponsiveness and deregulation of cell cycle components.


METHODS
Using isobologram analysis with MTT chemosensitivity testing, the effects of the CDK inhibitor seliciclib (CYC202, R-roscovitine) when used alone or in combination with paclitaxel was studied in uterine cancer cell lines. Apoptotic endpoints were also examined via Annexin V assay using flow cytometry and Western blotting.


RESULTS
Overall seliciclib combined with paclitaxel proved synergistic for all cell lines. This was concomitant with an enhanced apoptotic effect and downregulation of the LAP survivin.


CONCLUSIONS
Our data support the use of seliciclib as part of combination therapy for uterine cancer.
Coley
Helen M
HM
Postgraduate Medical School, University of Surrey, Guildford, Surrey GU2 7WG, UK. h.coley@surrey.ac.uk
Shotton
Christine F
CF
Thomas
Hilary
H
D017304:Annexin A5; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology*; D000077546:Roscovitine; D000077022:Survivin; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D017304:Annexin A5; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011687:Purines; D000077022:Survivin; D000077546:Roscovitine; D017239:Paclitaxel