It is well known that the imbalance between epithelial cell growth and inhibitor factors may cause human epithelial cancer. Over-expression of the epidermal growth factor receptor(EGFR) has been implicated in the development of oral squamous cell carcinoma. ZD1839 inhibits selectively the EGFR tyrosine kinase activity and is clinically used for cancer patients. However the mechanisms by which it exerts its anti-tumor activity remains unclear. This study attempted to determine the mechanisms underlying the effects of ZD1839 on the cellular level and to characterize the effects of ZD1839 with regard to human oral squamous cell carcinoma(OSCC) cell growth. The YD-10B and YD-38 cell lines established from OSCC in the department of Oral Pathology, Yonsei University College of Dentistry and ZD1839(Iressa) were used for this study. The inhibition of cell proliferation induced by ZD1839 was reversible and the lowest dose of ZD1839 that produced statistically significant growth inhibition in YD cell lines were 0.1 μM. The delay in cell cycle progression was induced by 0.1 μM of ZD1839 treatment after 24 hr. This reduction in cell proliferation and cell cycle delay were associated with up-regulation of the cyclin dependent kinase inhibitor(CDKI), P21CIP1/WAF1 and P27KIP1. Reduced expression of cyclin D1 was also observed after treatment with ZD 1839 to YD-38 cells but not to YD-38. The present results suggest that the antiproliferative effects of ZD1839, in vitro was associated with degradation of cyclin D1, which may be used as a possible indicator of a high cell sensitivity to ZD1839.

Background : Lutein, a xanthophyll, consists of chains with 8 conjugated double bounds containing closed rings on each end of the chain. This carotenoid is found in fruits and vegetables, especially dark green leafy vegetables such as green tea. In this study, we investigated the anticancer effects of purified lutein from green tea on human cancer cell lines containing prostate carcinoma cancer cells (LNCaP). Methods and Results : Prostate carcinoma cancer cells (LNCaP) were cultured and evaluated the inhibitory effect of lutein isolated from green tea compared other carotenoids (β-carotene and lycopene) on cell proliferation. Cyclin D1 and PCNA were evaluated as cell differentiation. In results, PCNA/cyclin regulates the initiation of cell proliferation by mediating DNA polymerase. Under cultural conditions, lycopene remarkably suppressed the PCNA expression prostate cancer cell line LNCaP in higher doses (20 μM - 100 μM) statistically. However, β-carotene and lutein presented the less inhibitory effects on PCNA expression. Determination of PCNA expression in control and treated cells demonstrates that lycopene did affect proliferation in LNCaP cancer cells in dose-dependent manner. However, β-carotene and lutein suppressed the cyclin D1 expression in dose-dependent manner but no in lycopene group. These results indicate that differ carotenoids presented the various suppressive ability of PCNA and cyclin D1 expression in cell proliferation. Conclusion : In conclusion, lutein suppressed the carcinogenesis of induced prostate cancer cell line by acting as a suppressor for inhibiting the expression of cyclin D.