INDUCED APOPTOSIS IN HUMAN PROSTATE CANCER CELL LINE LNCaP BY UKRAIN
ROUBLEVSKAIA I.N.,1 HAAKE A.R.,1,2 LUDLOW J.W.,2,3 POLEVODA B.V.3
1) Department of Dermatology, University of Rochester School
of Medicine and Dentistry, Rochester, USA.
2) University of Rochester Cancer Center, Rochester, USA.
3) Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, USA.
Address for correspondence: Bogdan V. Polevoda, Department
of Biochemistry and Biophysics, University of Rochester Medical Center, P.O.
Box 712, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Tel: 716-275-3329 Fax: 716-271-2683
Summary: Exposure of LNCaP prostate cancer cells to Ukrain (NSC-631570), a novel semisynthetic drug from Chelidonium majus L., results in cell growth inhibition which is concomitant with apoptosis. After 24 h treatment with 3.5 μΜ of Ukrain as many as 73% cells were found in the G2/M phase. However, at higher drug concentrations (7 μΜ and 17.5 μΜ) the changes in cell phase distribution were less dramatic but cell accumulation in the G2/M phase was still evident. The rate of apoptotic cells rose steadily with increased drug concentration in a dose-dependent manner and reached 20% at a dosage of 17.5 μΜ. To investigate whether the cell cycle control mechanisms are affected in response to Ukrain, we analyzed the expression levels of some cyclins, cyclin-dependent kinases (CDK) and apoptosis-related proteins in drug treated cancer cells. Western blot experiments revealed alterations in levels of CDK1 and CDK2, after treatment. Up-regulation of the CDK inhibitor p27 was observed, which may lead to G2/M cell accumulation, but no substantial changes in expression of Bcl-2 and Bax proteins were found.