CYSTATIN C IN LS LYMPHOSARCOMA AND HA-1 HEPATOMA TREATED WITH UKRAIN AND CYCLOPHOSPHAMIDE AND INVOLVEMENT OF APOPTOSIS

KOROLENKO T.A.,¹ POTERYAEVA O.N.,¹ DJANAYEVA S.J.,¹ SVECHNIKOVA I.G.,¹ KALEDIN V.I.,² TIMOFEYEVA O.A.,² FILIPENKO M.L.,² NOWICKY J.³

1) Institute of Physiology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia.
2) Institute of Bioorganic Chemistry, Siberian Branch of the Academy of Sciences, Novosibirsk, Russia.
3) Ukrainian Anticancer Institute, Vienna, Austria.

Address for correspondence: T.A. Korolenko, Institute of Physiology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, 630117, Russia.

Summary: The concentration of cystatin C, a cysteine proteinase inhibitor, was measured during the treatment of murine LS lymphosarcoma with cyclophosphamide and HA-1 murine hepatoma with the antitumor drug Ukrain. It was shown that concentrations of cystatin C were very low in both the tumor tissues studied (HA-1 hepatoma cells and LS lymphosarcoma); increased cystatin C concentrations were found only in Ukrain-treated murine hepatoma, suggesting the mechanism of antitumor effect of this drug. Cyclophosphamide treatment in LS lymphosarcoma did not influence the concentration of cystatin C in tumor cells. At the same time, a marked increase in cathepsin B and cathepsin L activity in LS lymphosarcoma was found, indicating the involvement of apoptosis in the mechanism of antitumor action of cyclophosphamide. While the DNA from untreated LS lymphosarcoma was very homogenous and its molecular weight was high, the DNA from tumors of treated mice broke down, giving rise to the ladder figure characteristically produced by cells dying from apoptosis. Evidence was obtained that cyclophosphamide-induced tumor regression was effected by apoptosis.