A new EGFR inhibitor induces apoptosis in colon cancer cells

• Published in: Biochemical and biophysical research communications Vol. 354; no. 2; pp. 409 - 413
• Main Authors: Calonghi, N., Pagnotta, E., Parolin, C., Mangano, C., Bolognesi, M.L., Melchiorre, C., Masotti, L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.03.2007
• Subjects: Apoptosis - drug effects; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - enzymology; Colonic Neoplasms - pathology; Confocal microscopy; Dose-Response Relationship, Drug; EGFR; HT29 Cells; Humans; Microscopy, Confocal; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - metabolism; Tyrosine kinase; Tyrosine kinase; Confocal microscopy; Colon cancer; EGFR
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.12.214

The use of agents targeting EGFR represents a new frontier in colon cancer therapy. Among these, mAbs and EGFR tyrosine kinase inhibitors seemed to be the most promising. However they have demonstrated scarce utility in therapy, the former being effective only at toxic doses, the latter resulting inefficient in colon cancer. This paper presents studies on a new EGFR inhibitor, FR18, a molecule containing the same naphtoquinone core as shikonin, an agent with great anti-tumor potential. In HT29, a human colon carcinoma cell line, flow cytometry, immunoprecipitation, and Western blot analysis, confocal spectral microscopy have demonstrated that FR18 is active at concentrations as low as 10nM, inhibits EGF binding to EGFR while leaving unperturbed the receptor kinase activity. At concentration ranging from 30nM to 5μM, it activates apoptosis. FR18 seems therefore to have possible therapeutic applications in colon cancer.