Endocrine Abstracts

Objective: Because the altered expression of superoxide dismutases, CuZn (SOD1) and Mn (SOD2) have been shown to constitute the basis of either resistance or susceptibility to the cytotoxic effect of various cytostatics and nucleoside drugs, we tested whether in human uterin cervix carcinoma cells (HeLaS3) the cytotoxic effect of cytostatics adriamycin (Adr), and cis-platinum (CP) or nucleoside drug, tiazofurin (TF) were involved in the activity of SOD1 and SOD2. Methods: Cytotoxicy was measured using the trypan blue (TBE) assay, and SOD1 and SOD2 protein expression by immunoblotting (dot blot) and presented as arbitrary units (AU).

Results: Treatment with Adr (0.1 micromolar) for 72 hr, significantly (p less than 0.001) stimulated SOD1 (control=100 AU plus/minus 9; Adr= 370 AU plus/minus 17, n=12) and SOD2 protein expression (control=100 AU plus/minus 8; Adr= 473 AU plus/minus 30, n=12). In addition, Adr had significant (p less than 0.001) citotoxic effect (81 plus/minus 4 percent, n=3). When HeLa cells were treated with CP (1 micromolar) for 72 hr, both proteins were significantly (p less than 0.001) stimulated by 5.3 plus/minus 1.2-fold (SOD1) and by 6.6 plus/minus 1.1 fold (SOD2). Cytotoxic effect induced by CP treatment was also significant (81 plus/minus 4 percent, n=6, p less than 0.001). We also detected that nucleoside drug TF (120 micromolar) applied for 72 hr, stimulates SOD1 (control=100 plus/minus 5; TF= 145 AU plus/minus 11, n=7, p less than 0.001) and SOD2 protein expression (control=100 plus/minus 2; TF= 169 AU plus/minus 4, n=7, p less than 0.001) with cytotoxic effect of 50 plus/minus 7 percent (p less than 0.001).

Conclusion: Our results indicate that the cytotoxic effect of Adr and CP are mediated via increased protein expression of SOD1 and SOD2 enzymes.