Antiproliferative effects of gefitinib are associated with suppression of E2F-1 expression and telomerase activity.. Mitsuhiro Suenaga; Akihiko Yamaguchi; Hiroshi Soda; Koji Orihara; Yuichi Tokito; Yoshimune Sakaki; Megumi Umehara; Kenji Terashi; Nakaaki Kawamata; Mikio Oka; Shigeru Kohno; Chuwa Tei (2006) Anticancer research display abstract
BACKGROUND: Gefitinib (Iressa, ZD1839) is a selective epidermal growth factor receptor tyrosine kinase inhibitor. E2F-1 is a critical determinant in cell cycle. Growth signals up-regulate telomerase activity. The effects of gefitinib on E2F-1 and telomerase in A549, H23 and A431 cells were examined. MATERIALS AND METHODS: Cell proliferation and cell cycle progression were measured by the WST-1 assay and flow cytometry. The expression of E2F-1 and cyclin-dependent kinase inhibitors was evaluated, and hTERT mRNA expression and telomerase activity were analyzed. RESULTS: In the A431 and A549 cells, treatment with gefitinib inhibited cell proliferation and was associated with an increase in G1-phase. In both cell types, gefitinib decreased the expression of E2F-1 mRNA and protein, followed by the suppression of hTERT mRNA and telomerase activity. In the H23 cells, gefitinib did not affect cell proliferation. CONCLUSION: The antiproliferative effects of gefitinib may be, at least in part, due to the inhibition of E2F-1 expression and telomerase activity.