BCL-2 OVEREXPRESSI0N PROTECTS HUMAN KERATINOCYTE CELLS FROM UKRAIN-INDUCED APOPTOSIS BUT NOT FROM G2/M ARREST
ROUBLEVSKAIA I.N.,1 HAAKE A.R.,1 POLEVODA B.V.2
1) Department of Dermatology, University of Rochester School
of Medicine and Dentistry, Rochester. New York, USA.
2) Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Address for correspondence: B. V. Polevoda, Department of Biochemistry and Biophysics, University of Rochester Medical Center, P.O. Box 712, 601 Elmwood Ave., Rochester, NY 14642, USA. Tel: 716-275-3329 Fax 716-271-2683 E-mail: Bogdan_Polevoda@urmc.rochester.edu
Summary: Exposure of ME180 and A431 carcinoma cells to Ukrain (NSC-631570), a semisynthetic compound consisting of alkaloids isolated from Chelidonium majus L. (Papaveracea), results in cell cycle arrest at the G2/M phase. Ukrain selectively inhibits growth of ME180 and A431 cells at a concentration range from 3.5 μΜ to 7.0 μΜ and induces apoptosis. In contrast, normal human keratinocytes showed no difference in the kinetics of progression through the cell cycle in response to this compound. We found that at a concentration of 7.0 μΜ of this drug Bcl-2 protein overexpression protected HaCaT cell line keratinocytes against apoptosis induced by Ukrain but did not prevent G2/M arrest. Following exposure of normal keratinocytes to Ukrain, we detected an increase in Bcl-2 protein levels and a significant change in protein modification as suggested by observation of its different isoform with shifted electrophoretic mobility. Bcl-2 protein expression and its isoform distribution did not change substantially in ΜΕ180 and A431 carcinoma cells. We also suggest that drug-induced mitotic arrest and apoptosis represent dual Ukrain action on cell cycle progression machinery and Bcl-2-involved program cell death in the cell.