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Targeting colon cancer cells with genistein-17.1A immunoconjugate
Michelle S Gentile1, Chenthamarakshan Vasu, Albert Green
1Department of Surgical Oncology, College of Medcine, University of Illinois at Chicago, Chicago, IL 60612, USA.
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.
Insights
Genistein, a soy compound, shows colon cancer benefits. Coupling it with the 17.1A antibody improved its anti-colon cancer activity and delivery to cancer cells.
Area of Science:
- Oncology
- Biochemistry
- Immunology
Background:
- Genistein, a soy isoflavone, exhibits anti-colon cancer properties in vitro.
- Achieving therapeutic genistein concentrations in serum is challenging.
- Monoclonal antibody 17.1A targets an antigen overexpressed in colon cancer.
Purpose of the Study:
- To enhance genistein's anti-colon cancer efficacy by conjugating it to the 17.1A antibody.
- To create a targeted delivery system for genistein in colon cancer treatment.
Main Methods:
- Genistein was conjugated to the 17.1A antibody using photochemical conjugation (sulfa-SANPAH).
- Purity of the conjugate (Gen-17.1A) was assessed via SDS-PAGE.
- Binding and internalization into colon cancer cells (SW-620, HT-29) were confirmed using flow cytometry and FITC-labeling.
- Apoptosis induction was evaluated using acridine orange/ethidium bromide staining.
Main Results:
- Gen-17.1A conjugate demonstrated specific binding and internalization into colon cancer cells.
- Gen-17.1A induced apoptosis in colon cancer cells.
- The conjugate significantly inhibited colon cancer cell growth both in vitro and in vivo.
Conclusions:
- Conjugating genistein to the 17.1A monoclonal antibody effectively enhances its anti-colon cancer activity.
- Gen-17.1A represents a promising targeted therapy for colon cancer.
- This approach overcomes limitations of achieving high genistein concentrations for effective cancer treatment.
