A novel approach of targeted ablation of mammary carcinoma cells through luteinizing hormone receptors using Hecate-CGbeta conjugate.
Recent studies have shown that human and animal mammary gland carcinoma cell line express luteinizing hormone receptors (LHRs). We have examined the cytotoxic effect of Hecate-CGbeta conjugate, that is, fusion of a lytic peptide (Hecate) and a 15-amino acid fragment of the CGbeta-chain in vitro. To test the hypothesis that the Hecate-CGbeta conjugate selectively abolishes cells possessing LHR, estrogen dependent and independent human breast cancer cell lines (MCF-7; MDA-MB-231) and a mouse Leydig tumor cell line (BLT-1) were treated in vitro with Hecate-CGbeta conjugate and Hecate alone. Cytotoxic effects of the Hecate-CGbeta conjugate and the Hecate alone was measured by lactate dehydrogenase (LDH) release immediately after treatment. We observed that the Hecate-CGbeta conjugate selectively, in dose-dependent manner destroys cells possessing LHR in lower concentrations of preparate comparing to the Hecate alone and that the cytotoxic effect is strongly correlated with the number of LHR. Using Western blot analysis we characterized the LHR on membranes of MDA-MB-231, MCF-7 and BLT-1 tumor cell lines. In addition, we showed the evaluation of inhibition potential of the Hecate-CGbeta conjugate to LHR. At a concentration of 33 microM the conjugate inhibited (50%; IC50) the binding of CG to LHR. We suggest further development of this novel approach for the treatment of breast cancer by the Hecate-CGbeta for in vivo trials.
Bodek
Gabriel
G
Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Rahman
Nafis Ahmed
NA
Zaleska
Monika
M
Soliymani
Rabah
R
Lankinen
Hikka
H
Hansel
William
W
Huhtaniemi
Ilpo
I
Ziecik
Adam J
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D007984:Leydig Cell Tumor / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008555:Melitten / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D011974:Receptors, LH / Q000187:drug effects* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; D011974:Receptors, LH; D011993:Recombinant Fusion Proteins; C098827:hecate 1; C480619:hecate-chorionic gonadotropin beta-subunit conjugate; D008555:Melitten; D007770:L-Lactate Dehydrogenase