Vasoactive intestinal peptide-camptothecin conjugates inhibit the proliferation of breast cancer cells

MOODY, Terry W ; MANTEY, Samuel A ; et al.

In: Vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide, Jg. 28 (2007), Heft 9, S. 1883-1890

academicJournal - print, 48 ref

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The effects of vasoactive intestinal peptide-camptothecin (VIP-CPT) conjugates were investigated on breast cancer cells and cells transfected with VIP receptors (R). (Ala2,8,9,19,24,25,27, Nle17, Lys28)VIP, (A-NL-K)VIP, was synthesized and Lys28 was coupled to a linker, N-methyl-amino-ethyl-glycine, L2, which formed a carbamate bond with CPT. The resulting (A-NL-K)VIP-L2-CPT was cytotoxic for MCF7 breast cancer cells, which have VPAC1-R, with IC50 values of 380 and 90 nM using the MTT and clonogenic assays, respectively. (A-NL-K)VIP, (A-NL-K)VIP-L2 and (A-NL-K)VIP-L2-CPT inhibited specific binding of125I-VIP to 3T3 cells transfected with VPAC1-R with IC50 values of 1.9, 56 and 126 nM, respectively. In contrast, (A-NL-K)VIP, (A-NL-K)VIP-L2 and (A-NL-K)VIP-L2-CPT inhibited specific binding of125I-Ro25-1553 to 3T3 cells transfected with VPAC2-R with IC50 values of 3.9, 3162 and 2690 nM, respectively. (A-NL-K)VIP, (A-NL-K)VIP-L2 and (A-NL-K)VIP-L2-CPT caused increased cAMP after addition to MCF7 cells. 125I-(A-NL-K)VIP-L2-CPT was internalized by MCF7 cells at 37 °C but not 4 °C. These results indicate that (A-NL-K)VIP-L2-CPT is a VPAC1-R agonist which is cytotoxic for breast cancer cells.

Titel:	Vasoactive intestinal peptide-camptothecin conjugates inhibit the proliferation of breast cancer cells
Autor/in / Beteiligte Person:	MOODY, Terry W ; MANTEY, Samuel A ; FUSELIER, Joseph A ; COY, David H ; JENSEN, Robert T
Link:	E-Journal im Bestand der UB Hagen? View record from PASCAL Archive
Zeitschrift:	Vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide, Jg. 28 (2007), Heft 9, S. 1883-1890
Veröffentlichung:	New York, NY: Elsevier Science, 2007
Medientyp:	academicJournal
Umfang:	print, 48 ref
ISSN:	0196-9781 (print)
Schlagwort:	Biochemistry, molecular biology, biophysics Biochimie, biologie moléculaire, biophysique Endocrinology Endocrinologie Neurology Neurologie Sciences biologiques et medicales Biological and medical sciences Sciences biologiques fondamentales et appliquees. Psychologie Fundamental and applied biological sciences. Psychology Vertebres: endocrinologie Vertebrates: endocrinology Sciences medicales Medical sciences Gynecologie. Andrologie. Obstetrique Gynecology. Andrology. Obstetrics Pathologie de la glande mammaire Mammary gland diseases Tumeurs Tumors Alcaloïde Alkaloid Alcaloide DNA topoisomerase Enzyme Enzima Glande mammaire pathologie Glándula mamaria patología Inhibiteur enzyme Enzyme inhibitor Inhibidor enzima Isomerases Tumeur maligne Malignant tumor Tumor maligno Camptothécine Cytotoxicité Cytotoxicity Citotoxicidad Multiplication cellulaire Cell proliferation Multiplicación celular Récepteur VIP VIP receptor Receptor VIP Récepteur biologique Biological receptor Receptor biológico VIP Vasoactive intestinal peptide Cancer du sein Breast cancer Cáncer de pecho Inhibiteur de la topoisomérase I Camptothecin,VIP receptors,Cellular proliferation,Breast cancer,Receptor-mediated cytotoxicity
Sonstiges:	Nachgewiesen in: PASCAL Archive Sprachen: English Original Material: INIST-CNRS Document Type: Article File Description: text Language: English Author Affiliations: Department of Health and Human Services, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, United States ; Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, United States ; Department of Medicine, Peptide Research Labs, Tulane Health Sciences Center, New Orleans, LA 70112, United States Rights: Copyright 2007 INIST-CNRS ; CC BY 4.0 ; Sauf mention contraire ci-dessus, le contenu de cette notice bibliographique peut être utilisé dans le cadre d’une licence CC BY 4.0 Inist-CNRS / Unless otherwise stated above, the content of this bibliographic record may be used under a CC BY 4.0 licence by Inist-CNRS / A menos que se haya señalado antes, el contenido de este registro bibliográfico puede ser utilizado al amparo de una licencia CC BY 4.0 Inist-CNRS Notes: Gynecology. Andrology. Obstetrics ; Vertebrates : endocrinology

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