DECREASE IN TUMORIGENIC ACTIVITY OF MURINE HEPATOMA CELLS AFTER TREATMENT WITH ANTIOXIDANTS AND MELATONIN
N. A. Filatova, K. M. Kirpichnikova, N. D. Aksenov, E. A. Vakhromova, I. A. Gamaley 1
Institute of Cytology RAS, St. Petersburg;
1 e-mail: igamaley@mail.cytspb.rssi.ru
We studied the effect of antioxidants such as N-acetylcysteine (NAC, 10 mM) and alpha-lipoic acid (ALA, 1.25 mM) and of the hormone melatonin (1 ìM) on the ability of murine
hepatoma cells MH22a to develop tumors in syngenic mice (C3HA) after subsutaneous injection. Tumor formation and development slowed down and mouse mortality decreased when
the injected cells were pretreated by NAC, ALA or melatonin during 20 h. Melatonin had the most marked effect. Tumors appeared in 100 % cases after 10 days in control mice when
untreated cells had been injected; injection of cells pretreated by NAC or ALA resulted in tumor formation only in 40 and 53 % of mice, respectively. When cells were pretreated with
melatonin the tumors appeared only in 18-20 days after injection. Until the end of the observation (36 days) 67 % of control mice died, but when the cells were pretreated by NAC or
ALA mouse death-rate was 20 and 53 %, respectively. In the case of melatonin we did not observed any dead mice at all. We showed that treatment by antioxidants delayed (NAC)
or completely inhibited (ALA) cell cycle of hepatoma cells. Cell cycle was restored after removal of the antioxidants. Melatonin did not change cell cycle phase distribution. We conclude
that there is no direct correlation between loss of tumorigenic properties and changing of proliferative activity of hepatoma cells. Different mechanisms of an-tioxidants and melatonin action
resulting in transient tumor phenotype normalization are discussed.
Key words: tumorigenic cells MH22a, murine hepatoma, N-acetylcysteine, alpha-lipoic acid, melatonin, cell cycle
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