Considering the problems involved in prevention of human
lung cancer, growth inhibition of human
lung cancer cell line A549 was studied with emphasis on two parameters:
green tea polyphenols, such as (-)-
epigallocatechin gallate (EGCG) and (-)-
epicatechin gallate (ECG); and
heterogeneous nuclear ribonucleoprotein B1 (
hnRNP B1), a new
biomarker of human
lung cancer which is highly expressed in the very early stages of human
lung cancer. The inhibitory potencies of
green tea polyphenols were compared with those of
genistein as a control. EGCG or ECG and
genistein as a control dose-dependently inhibited the growth of A549 cells, which strongly elevated
hnRNP B1 protein, and increased G2/M phase cells associated with induction of apoptotic cells. The results were confirmed by previous evidence with human
lung cancer cell line PC-9. Some larger differences in mechanisms of action between
green tea polyphenols and
genistein were presented. Treatment of A549 cells with EGCG, ECG or
genistein significantly inhibited the expression levels of
hnRNP B1 mRNA and the elevated levels of
hnRNP B1 protein, both of which are constitutively elevated in
cancer cells. Furthermore, both EGCG and
genistein inhibited the promoter activity of
hnRNP A2/B1 gene expression, with IC50 values 29 microM for EGCG and 66 microM for
genistein, suggesting the interaction of EGCG or
genistein with the transcriptional complex. Looking at our results here, and those of previously reported epidemiological studies with
green tea, we discuss the steadily accumulating evidence that clinical trials with
green tea extract would be an efficient means of
lung cancer prevention.