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  • Title: The development of VIP-ellipticine conjugates.
    Author: Moody TW, Czerwinski G, Tarasova NI, Moody DL, Michejda CJ.
    Journal: Regul Pept; 2004 Dec 15; 123(1-3):187-92. PubMed ID: 15518911.
    Abstract:
    The mechanism by which vasoactive intestinal peptide (VIP)-ellipticine (E) conjugates are cytotoxic for human lung cancer cells was investigated. VIP-alanyl-leucyl-alanyl-leucyl-alanine (ALALA)-E and VIP-leucyl-alanyl-leucyl-alanine (LALA)-E inhibited (125)I-VIP binding to NCI-H1299 cells with an IC50 values of 0.5 and 0.1 microM, respectively. VIP-ALALA-E and VIP-LALA-E caused elevation of cAMP in NCI-H1299 cells with ED50 values of 0.7 and 0.1 microM. Radiolabeled VIP-LALA-E was internalized at 37 degrees C and delivered the cytotoxic E into NCI-H1299 cells. VIP-LALA-E inhibited the growth of NCI-H1299 cells in vitro. Three days after the addition of VIP-LALA-E to NCI-H1299 cells, cell viability decreased based on trypan blue exclusion and reduced 3H-thymidine uptake. These results suggest that VIP-E conjugates are internalized in lung cancer cells as a result of VPAC1 receptor-mediated endocytosis.
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