22. 4 respectively. The apoptotic index induced by CIS alone in HeLa and SiHa cells were slightly lower than those obtained with PTX alone, but higher than those of untreated tumor cells, respec tively. Interestingly, the most important indexes of apoptosis were obtained with the combina tion of PTX CIS reaching for HeLa an apoptotic for index of 59. 81. 8 and for SiHa cells 47. 22. 9. In contrast, in HaCaT cells treated with PTX, CIS or its combination, apoptotic indexes were similar to those untreated cells. It is well known that caspases play a central role in apoptosis, because that we studied the caspases activa tion pathways. Participation of caspases 3, 6, 7 and 9 was determined by flow cytometry using M30 antibody. In Figure 1B it can be observed that the three untreated cells lines displayed minimal caspases activity.

Inhibitors,Modulators,Libraries PTX culture exposure increases by 17. 2 times the per centage of M30 positive cells in HeLa and by 5. 8 times in SiHa. CIS induces an increase of caspase activation in HeLa cells of 6. 2 times higher than in untreated cells and had no effect in SiHa cells. However, in PTX CIS treated cells, we found a clear additive effects in both cervical tumor cell lines, observing a increment of positive cells to caspase Inhibitors,Modulators,Libraries activ ity of 23. 3 and 6. 5 times higher, respectively, than of untreated control cells. In Figure 1C, it can observe that untreated group of HeLa and SiHa cells displayed minimal caspase 8 activ ity, but when these cells were treated with PTX, we found increments of caspase 8 activity to be 4. 2 and 2.

7 fold higher in HeLa and SiHa cells, respectively, Inhibitors,Modulators,Libraries also CIS alone induces an increase of caspase 8 activity but lower that the incre ment induced by PTX. The higher increments on caspase 8 activity was found in PTX CIS treated groups were this treatment HeLa and SiHa reached increments of Inhibitors,Modulators,Libraries 5. 1 and 3. 2 times higher than the CIS treated group. PTX decreases CIS induced senescence Senescence was measured by determination Inhibitors,Modulators,Libraries of the b galactosidase. In all untreated cell lines studied, the percentage of senescence was minimum. It is noteworthy that PTX does not induce senescence in all cell lines. In opposite fashion, CIS induced high levels of senescence in comparison with untreated control cells 6. 9 times higher in HeLa and in SiHa cells, and in both cases P 0. 001 vs the untreated control group. CIS does not modify selleck screening library the percentage of senescence in HaCaT cells. In HeLa and SiHa cells treated with PTX CIS the per centage of SA b Gal was significantly lower which represents a 3. 6 and 3 times lower diminution in relationship to senescence induced by CIS alone. Total I Ba and I Ba Phosphorylated in serine 32 As a central point, in this set of experiments we quantified the total I Ba and the phosphorylated form.