We selected cells, where doxorubicin is typically applied and which overexpress somatostatin receptors, like the human pancreatic carcinoma cell line MIA PaCa-2 or MCF-7. Doxorubicins antiproliferative action on MIA PaCa-2 after 72 h incubation with the drug was as expected very strong (IC50 = 0.80 ± 0.13 μM), whereas octreotide was not able to inhibit cell growth by 50% up to a concentration of 150 μM. The cytotoxic effects of the conjugate expressed, as half maximal inhibitory concentration was much stronger compared to the precursor peptide, but, nevertheless, lower than that of doxorubicin (IC50 = 31.50 ± 1.74 μM). This characteristic feature of 12 is attributed to the different cellular uptake mechanisms of the substances. Doxorubicin is taken up quickly by passive diffusion, while octreotide enters cells by receptor-mediated endocytosis. Furthermore, it needs to be considered that the conjugate releases after cleavage by glutathione a doxorubicin derivative, which is still carrying a small cross-linker residue. Previous studies have shown that these types of molecules are, nevertheless, capable of successfully interacting with DNA, to mediate their cytotoxic properties, but to a lesser extent.

We selected cells, where doxorubicin is typically applied and which overexpress somatostatin receptors, like the human pancreatic carcinoma cell line MIA PaCa-2 or MCF-7. Doxorubicins antiproliferative action on MIA PaCa-2 after 72 h incubation with the drug was as expected very strong (IC50 = 0.80 ± 0.13 μM), whereas octreotide was not able to inhibit cell growth by 50% up to a concentration of 150 μM. The cytotoxic effects of the conjugate expressed, as half maximal inhibitory concentration was much stronger compared to the precursor peptide, but, nevertheless, lower than that of doxorubicin (IC50 = 31.50 ± 1.74 μM). This characteristic feature of 12 is attributed to the different cellular uptake mechanisms of the substances. Doxorubicin is taken up quickly by passive diffusion, while octreotide enters cells by receptor-mediated endocytosis. Furthermore, it needs to be considered that the conjugate releases after cleavage by glutathione a doxorubicin derivative, which is still carrying a small cross-linker residue. Previous studies have shown that these types of molecules are, nevertheless, capable of successfully interacting with DNA, to mediate their cytotoxic properties, but to a lesser extent.

We selected cells, where doxorubicin is typically applied and which overexpress somatostatin receptors, like the human pancreatic carcinoma cell line MIA PaCa-2 or MCF-7. Doxorubicins antiproliferative action on MIA PaCa-2 after 72 h incubation with the drug was as expected very strong (IC50 = 0.80 ± 0.13 μM), whereas octreotide was not able to inhibit cell growth by 50% up to a concentration of 150 μM. The cytotoxic effects of the conjugate expressed, as half maximal inhibitory concentration was much stronger compared to the precursor peptide, but, nevertheless, lower than that of doxorubicin (IC50 = 31.50 ± 1.74 μM). This characteristic feature of 12 is attributed to the different cellular uptake mechanisms of the substances. Doxorubicin is taken up quickly by passive diffusion, while octreotide enters cells by receptor-mediated endocytosis. Furthermore, it needs to be considered that the conjugate releases after cleavage by glutathione a doxorubicin derivative, which is still carrying a small cross-linker residue. Previous studies have shown that these types of molecules are, nevertheless, capable of successfully interacting with DNA, to mediate their cytotoxic properties, but to a lesser extent.