Targeting colon cancer cells with genistein-17.1A immunoconjugate.
We have shown that genistein, a major component of soy, has anti-colon cancer effects in vitro. These effects are attainable at high concentrations that are difficult to achieve in the serum. The purpose of this study was to enhance the activity of genistein against colon cancer cells by coupling it to 17.1A. The monoclonal antibody 17.1A recognizes an epithelial membrane antigen that is overexpressed in colon cancer. Synthesis of Gen-17.1A was achieved by photochemical conjugation using sulfa-SANPAH. Its purity was evaluated by SDS-PAGE. Binding of Gen-17.1A to SW-620 and HT-29 cells was shown using flow cytometry. Internalization was demonstrated by FITC-labeling. Gen-17.1A induced apoptosis in colon cancer cells as evidenced by the acridine orange/ethidium bromide staining method. Gen-17.1A significantly inhibited colon cancer cell growth in vitro and in vivo. Our findings suggest that conjugating genistein to 17.1A monoclonal antibody enhances its effects against colon cancer cells.
Gentile
Michelle S
MS
Department of Surgical Oncology, College of Medcine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Vasu
Chenthamarakshan
C
Green
Albert
A
Murillo
Genoveva
G
Das Gupta
Tapas K
TK
Constantinou
Andreas I
AI
Prabhakar
Bellur S
BS
Salti
George I
GI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D001692:Biological Transport; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D019833:Genistein / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; C476210:genistein-17.1A immunoconjugate; D019833:Genistein