Antibodies directed against L1-CAM synergize with Genistein in inhibiting growth and survival pathways in SKOV3ip human ovarian cancer cells

Cancer Lett. 2008 Mar 18;261(2):193-204. doi: 10.1016/j.canlet.2007.11.012. Epub 2007 Dec 26.

Abstract

Antibodies directed against the L1 cell adhesion protein inhibit growth of SKOV3ip human ovarian cancer cells in vitro and in vivo. Responses of SKOV3ip cells in vitro to anti-L1 mAb chCE7 and Genistein were investigated. Genistein potentiated the anti-proliferative and pro-apoptotic effects of chCE7 in SKOV3ip cells. A combination of mAb chCE7 and Genistein strongly reduced the sensitivity of p44/42 (Erk1,2) kinase, Src kinase and Akt kinase to extracellular stimulation with serum, Epidermal Growth Factor and Hepatocyte Growth Factor. The observed synergy of antibodies directed against L1 with Genistein could lead to a new therapeutic option for ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / immunology
  • Blotting, Western
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • DNA Primers
  • Drug Synergism
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors
  • Female
  • Genistein / pharmacology*
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neural Cell Adhesion Molecule L1 / immunology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • src-Family Kinases / metabolism

Substances

  • Antibodies, Monoclonal
  • Anticarcinogenic Agents
  • DNA Primers
  • Neural Cell Adhesion Molecule L1
  • RNA, Messenger
  • Epidermal Growth Factor
  • Hepatocyte Growth Factor
  • Genistein
  • ErbB Receptors
  • src-Family Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3