title: A matrix metalloproteinase 2 cleavable melittin/avidin conjugate specifically targets tumor cells in vitro and in vivo.
abstract: Extracellular matrix breakdown as well as increased expression in cancer cells and tumor microvascular endothelial cells make matrix metalloproteinase 2 (MMP2) an attractive target for cancer treatment. By taking advantage of MMP2's properties, an MMP2 cleavable melittin/avidin conjugate was designed. Melittin alone is extremely toxic to cells and induces immediate cell lysis, but becomes inactive when coupled with avidin. The incorporation of the MMP2 target sequence into the peptide was used as a means for targeting tumor cells. In vitro, the melittin/avidin conjugate showed strong cytolytic activity against cancer cells with high MMP2 activity; DU 145 prostate cancer cells and SK-OV-3 ovarian cancer cells. The conjugate exhibited very little cytolytic activity against normal L-cells that displayed low MMP2 activity. These data demonstrate the MMP2 specificity of the melittin/avidin conjugate. In vivo, the size of tumors injected with the melittin/avidin conjugate was significantly smaller as compared to untreated tumors. Therefore, due to its tumor targeting capabilities as well as its cytolytic properties in vitro and in vivo, the melittin/avidin conjugate displays the potential for use in cancer therapy.
authors.affiliation: Department of Biological Science, Clemson University, Clemson, SC 29634, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Holle
authors.forename: Wendy
authors.initials: W
authors.lastname: Song
authors.forename: Eric
authors.initials: E
authors.lastname: Holle
authors.forename: Yanzhang
authors.initials: Y
authors.lastname: Wei
authors.forename: Thomas
authors.initials: T
authors.lastname: Wagner
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001360:Avidin / Q000008:administration & dosage* / Q000378:metabolism; D002460:Cell Line; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D008555:Melitten / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D000970:Antineoplastic Agents; D001360:Avidin; D008555:Melitten; D007770:L-Lactate Dehydrogenase; D020778:Matrix Metalloproteinase 2