Search

The confluence-dependent resistance of human larynx carcinoma HEp-2 cells to hydrogen peroxide and a new antitumor drug based on the combination of vitamins C and B12b was studied. It was found that this resistance in growing cells is suppressed by the disruption of intercellular contacts by EGTA and is related neither to the activity of P-glycoprotein nor to the content of intracellular glutathione and the activities of glutathione S-transferases, glutathione peroxidase and glutathionine reductase. Here we showed that the level of expression of the small heat shock protein hsp27, which is known to protect cells from a variety of stresses associated with apoptosis, in growing confluent cells both in the presence and absence of the vitamins B12b and C is much higher (about 20-25 times) than in non-confluent cells. Taken together, the results suggest that the confluence-dependent resistance of cells to the combination of vitamins C and B12b and to hydrogen peroxide is mediated by hsp27 overexpression, which is activated via cell-cell adhesion.

The combination of hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C) can cause the death of tumor cells at the concentrations of the components at which they are nontoxic when administered separately. This cytotoxic action on epidermoid human larynx carcinoma cells HEp-2 in vitro is shown to be due to the hydrogen peroxide generated by the combination of vitamins B12b and C. The drop in the glutathione level preceding cell death was found to be the result of combined action of the vitamins. It is supposed that the induction of cell death by combined action of vitamins B12b and C is connected to the damage of the cell redox system.