We studied the effects of fibroblast growth factor (FGF‐10) on H2O2‐induced alveolar epithelial cell (AEC) G1 arrest and the role of G1 cyclins. FGF‐10 prevented H2O2‐induced AEC G1 arrest. FGF‐10 induced 2–4‐fold increase in cyclin E, cyclin A and CDKs (2, 4) alone and in AEC treated with H2O2. H2O2 downregulated cyclin D1; FGF‐10 blocked these effects. FGF‐10 prevented H2O2‐induced upregulation of CDK inhibitor, p21. SiRNAp21 blocked H2O2‐induced downregulation of cyclins, CDKs and AEC G1 arrest. Accordingly, we provide first evidence that FGF‐10 regulates G1 cyclins and CDKs, and prevents H2O2‐induced AEC G1 arrest.

Triptolide (PG490), a diterpene triepoxide, is a potent immunosuppressive agent extracted from the Chinese herb Tripterygium wilfordii. We have previously shown that triptolide blocks NF-kappaB activation and sensitizes tumor necrosis factor (TNF-alpha)-resistant tumor cell lines to TNF-alpha-induced apoptosis. We show here that triptolide enhances chemotherapy-induced apoptosis. In triptolide-treated cells, the expression of p53 increased but the transcriptional function of p53 was inhibited, and we observed a down-regulation of p21(waf1/cip1), a p53-responsive gene. The increase in levels of the p53 protein was mediated by enhanced translation of the p53 protein. Additionally, triptolide induced accumulation of cells in S phase and blocked doxorubicin-mediated accumulation of cells in G(2)/M and doxorubicin-mediated induction of p21. Our data suggest that triptolide, by blocking p21-mediated growth arrest, enhances apoptosis in tumor cells.