As shown in Table 1, the cytotoxic potency of the tubugi-1-SH was - in case of HT-29 and PC-3 - by factors 5 to 8 higher compared to the entire peptide-toxin conjugate 8. The only slight increase of cytotoxic activity of compound 9 compared to the complete conjugate 8 in Colo320 cells is most likely caused by a generally weak responsiveness of Colo320 cells towards tubugi-1-SH and the entire conjugate tubugi-1-SS-NPY. When compared with HT-29 and PC-3 cells, the IC50 value of tubugi-1-SH is by factor 10 higher in Colo320. Since the membrane passage of tubugi-1-SH is not depending on a NPY receptor, there have to be other explanations for the reduced cytotoxic impact of tubugi-1 and corresponding derivatives in Colo320, rather than the NPY Y1 receptor expression level.

As shown in Table 1, the cytotoxic potency of the tubugi-1-SH was - in case of HT-29 and PC-3 - by factors 5 to 8 higher compared to the entire peptide-toxin conjugate 8. The only slight increase of cytotoxic activity of compound 9 compared to the complete conjugate 8 in Colo320 cells is most likely caused by a generally weak responsiveness of Colo320 cells towards tubugi-1-SH and the entire conjugate tubugi-1-SS-NPY. When compared with HT-29 and PC-3 cells, the IC50 value of tubugi-1-SH is by factor 10 higher in Colo320. Since the membrane passage of tubugi-1-SH is not depending on a NPY receptor, there have to be other explanations for the reduced cytotoxic impact of tubugi-1 and corresponding derivatives in Colo320, rather than the NPY Y1 receptor expression level.

As shown in Table 1, the cytotoxic potency of the tubugi-1-SH was - in case of HT-29 and PC-3 - by factors 5 to 8 higher compared to the entire peptide-toxin conjugate 8. The only slight increase of cytotoxic activity of compound 9 compared to the complete conjugate 8 in Colo320 cells is most likely caused by a generally weak responsiveness of Colo320 cells towards tubugi-1-SH and the entire conjugate tubugi-1-SS-NPY. When compared with HT-29 and PC-3 cells, the IC50 value of tubugi-1-SH is by factor 10 higher in Colo320. Since the membrane passage of tubugi-1-SH is not depending on a NPY receptor, there have to be other explanations for the reduced cytotoxic impact of tubugi-1 and corresponding derivatives in Colo320, rather than the NPY Y1 receptor expression level.

The 72 h treatment is more effective than the 6 h pulse treatment. Notably, in vitro antitumor activities of 8 were found to correlate very good with the hY1R expression levels, as detected by gene expression analyses using RT-qPCR. Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal breast cell line 184B5 is in the same order of magnitude as for the hY1R-deficient tumor cell line (MDA-MB-231), both tested at even higher concentration of the PDC than for the Y1 cell lines.

The 72 h treatment is more effective than the 6 h pulse treatment. Notably, in vitro antitumor activities of 8 were found to correlate very good with the hY1R expression levels, as detected by gene expression analyses using RT-qPCR. Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal breast cell line 184B5 is in the same order of magnitude as for the hY1R-deficient tumor cell line (MDA-MB-231), both tested at even higher concentration of the PDC than for the Y1 cell lines.

The 72 h treatment is more effective than the 6 h pulse treatment. Notably, in vitro antitumor activities of 8 were found to correlate very good with the hY1R expression levels, as detected by gene expression analyses using RT-qPCR. Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal breast cell line 184B5 is in the same order of magnitude as for the hY1R-deficient tumor cell line (MDA-MB-231), both tested at even higher concentration of the PDC than for the Y1 cell lines.

The 72 h treatment is more effective than the 6 h pulse treatment. Notably, in vitro antitumor activities of 8 were found to correlate very good with the hY1R expression levels, as detected by gene expression analyses using RT-qPCR. Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal breast cell line 184B5 is in the same order of magnitude as for the hY1R-deficient tumor cell line (MDA-MB-231), both tested at even higher concentration of the PDC than for the Y1 cell lines.

The 72 h treatment is more effective than the 6 h pulse treatment. Notably, in vitro antitumor activities of 8 were found to correlate very good with the hY1R expression levels, as detected by gene expression analyses using RT-qPCR. Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal breast cell line 184B5 is in the same order of magnitude as for the hY1R-deficient tumor cell line (MDA-MB-231), both tested at even higher concentration of the PDC than for the Y1 cell lines.

The 72 h treatment is more effective than the 6 h pulse treatment. Notably, in vitro antitumor activities of 8 were found to correlate very good with the hY1R expression levels, as detected by gene expression analyses using RT-qPCR. Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal breast cell line 184B5 is in the same order of magnitude as for the hY1R-deficient tumor cell line (MDA-MB-231), both tested at even higher concentration of the PDC than for the Y1 cell lines.

The 72 h treatment is more effective than the 6 h pulse treatment. Notably, in vitro antitumor activities of 8 were found to correlate very good with the hY1R expression levels, as detected by gene expression analyses using RT-qPCR. Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal breast cell line 184B5 is in the same order of magnitude as for the hY1R-deficient tumor cell line (MDA-MB-231), both tested at even higher concentration of the PDC than for the Y1 cell lines.

The 72 h treatment is more effective than the 6 h pulse treatment. Notably, in vitro antitumor activities of 8 were found to correlate very good with the hY1R expression levels, as detected by gene expression analyses using RT-qPCR. Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal breast cell line 184B5 is in the same order of magnitude as for the hY1R-deficient tumor cell line (MDA-MB-231), both tested at even higher concentration of the PDC than for the Y1 cell lines.