Induced G2/M Arrest and Apoptosis in Human Epidermoid Carcinoma Cell Lines by Semisynthetic Drug Ukrain

INNA N. ROUBLEVSKAIA¹, BOGDAN V. POLEVODA², JOHN W. LUDLOW^2,3 and ANNE R. HAAKE^1,3

¹Department of Dermatology,
²Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, and
³University of Rochester Cancer Center, Rochester NY 14642, U.S.A.

Correspondence to: B.V. Polevoda, Dept. of Biochemistry and Biophysics, University of Rochester Medical Center, P.O. Box 712, 601 Elmwood Ave., Rochester, NY 14642 U.S.A. Tel 716-275-3329; Fax 716-271-2683. E-mail: Bogdan_Polevoda@urmc.rochester.edu

Key Words: Apoptosis, cell-cycle, G2/M arrest, p27, Ukrain.

Abstract. Exposure of ME 180 and A431 carcinoma cells to Ukrain (NSC-631570), a novel semisynthetic drug from Chelidonium majus L, results in cell growth inhibition which is concomitant with reversible G2/M cell cycle arrest and apoptosis at doses as low as 7 μΜ. In contrast, the same drug concentrations were not affective towards normal human keratinocytes. In order to investigate whether cell cycle control mechanisms are effected in response to Ukrain, we analyzed cell cycle distribution and levels of cyclins and cyclindependent kinases in drug treated carcinoma cells. We found alterations in levels of mitotic cyclins A and B1, and cyclindependent kinases CDK1 and CDK2, after treatment. We also observed an upregulation of CDK inhibitor p27 in both cancer cell lines which may lead to the G2/M cells accumulation.