The development of VIP–ellipticine conjugates

The development of VIP–ellipticine conjugates

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 125I-VIP binding to NCI-H1299 cells with an IC50...

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Bibliographic Details
Published in:Regulatory peptides Vol. 123; no. 1-3; pp. 187 - 192
Main Authors: Moody, Terry W., Czerwinski, Gregory, Tarasova, Nadia I., Moody, Deborah L., Michejda, Christopher J.
Format: Journal Article Conference Proceeding
Language:English
Published: Shannon Elsevier B.V 15-12-2004
Amsterdam Elsevier
Subjects:
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation - drug effects
Cyclic AMP - biosynthesis
Drug Design
Ellipticines - chemical synthesis
Ellipticines - chemistry
Ellipticines - pharmacokinetics
Ellipticines - pharmacology
Endocytosis
Humans
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Medical sciences
Pneumology
Receptors, Vasoactive Intestinal Peptide - agonists
Receptors, Vasoactive Intestinal Peptide - metabolism
Receptors, Vasoactive Intestinal Polypeptide, Type I
Thymidine - metabolism
Tumors of the respiratory system and mediastinum
Vasoactive Intestinal Peptide - chemical synthesis
Vasoactive Intestinal Peptide - chemistry
Vasoactive Intestinal Peptide - pharmacokinetics
Vasoactive Intestinal Peptide - pharmacology
VIP agonists
VIP–ellipticine derivatives
VPAC1 receptor
PACAP
E
Lung cancer
VIP–ellipticine derivatives
G
alanyl-leucyl-alanyl-leucyl-alanine
LALA
ellipticine
hyb
VIP agonists
VPAC1 receptor
vasoactive intestinal peptide
leucyl-alanyl-leucyl-alanine
pituitary adenylate cyclase activating polypeptide
hybrid
glycine
VIP
ALALA
Lung disease
Agonist
Respiratory disease
In vitro
Cell line
Vasoactive intestinal peptide
Development
VPACI receptor
VIP-ellipticine derivatives
Conjugated compound
Biological receptor
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Summary: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 125I-VIP binding to NCI-H1299 cells with an IC50 values of 0.5 and 0.1 μM, 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 μM. Radiolabeled VIP–LALA–E was internalized at 37 °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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SourceType-Scholarly Journals-1
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content type line 23
ISSN:0167-0115
1873-1686
DOI:10.1016/j.regpep.2004.03.021