Targeting colon cancer cells with genistein-17.1A immunoconjugate.

Abstract

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.

• Authors: Michelle S Gentile, Chenthamarakshan Vasu, Albert Green, Genoveva Murillo, Tapas K Das Gupta, Andreas I Constantinou, Bellur S Prabhakar, George I Salti
• Journal: International journal of oncology (Int J Oncol) Vol. 22 Issue 5 Pg. 955-9 (May 2003) ISSN: 1019-6439 [Print] Greece
• PMID: 12684659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Immunoconjugates
• genistein-17.1A immunoconjugate
• Genistein

Topics

• Animals
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use, toxicity)
• Antineoplastic Agents (pharmacokinetics, toxicity)
• Apoptosis (drug effects)
• Binding Sites
• Biological Transport
• Cell Membrane (drug effects, metabolism)
• Colonic Neoplasms (drug therapy, pathology)
• Genistein (analogs & derivatives, pharmacokinetics, therapeutic use, toxicity)
• Humans
• Immunoconjugates (pharmacokinetics, therapeutic use, toxicity)
• Mice
• Mice, Nude
• Transplantation, Heterologous
• Tumor Cells, Cultured