Objective: To study the effect of active compound 6F and A from Pteris semipinnata L.(PsL) on the activities of DNA topoisomerase (TOPO) I and lI, activities of cytosolic and membrane TPK, and expression of oncogene c-myc in lung adenocarcinoma cells. Methods: The effect of compound 6F and A on activities of cytosolic and membrane TPK was measured by scintillation counting; the effect of compound A on expression of oncogene c-myc was determined by flow cytometry indirect fluorimetry. Results: compound 6F and A could inhibit the activities of TOPO I, and they strongly inhibited the TOPO II in 0.01 mg/L and 10.0 mg/L respectively. Compound A slightly inhibited the activities of membrane TPK, but not the cytosolic one. Compound A could inhibit the expression of oncogene c-myc. Conclusion: Topoisomerases are target of compound 6F and A. Compound A could slightly inhibit the activities of TPK, and showed an inhibitory effect on the expression of oncogene c-myc. Tyrosine protein kinase, c-mycTopoisomerases are key nuclear enzymes, which play critical role during cell growth. They alter DNA topology and adjust the conformation of DNA molecules by strand breakage and rejoining. Two types have been identified, topoisomerase I (TOPO I) and topoisomerase II (TOPO II). TOPO I breaks the single DNA strands by trapping the enzyme in an incovalent bond form with its DNA substrate, and it is an ATP-independent enzyme. TOPO II affect DNA replication through inducing a transient breakage of single or double DNA strands and then rejoining the strand break, it needs ATP to provide energy in the reaction catalyzed r11. It was reported that most of the TOPO I and/or TOPO II inhibitors were important clinically used antineoplastic agents, such as camptothecin(CPT), doxorubicin, etoposide (Vp-16), and 4'-[9-acridinylamino]-N-[methane-sulfonyl]-m-anisidine] (m-AMSA) ~241. They catalyze single or double DNA breakage by intercalating or nonintercalating to DNA, and then interfere with the function of enzymes. Tyrosine protein kinase (TPK) is a kinase which phosphorylates the tyrosine residue in protein. It was proved that TPK was associated with cell proliferation, differentiation, oncogene activation, and signal transduction Es6~. Both of TOPOI and TOPO II are TPK's substrates in vitro. Some compounds which were considered as specific TPK inhibitors were also TOPOI and/or TOPO II inhibitors.Pteris semipinnata L (PsL) is a Chinese traditional herb. Its extract showed obvious antitumor activity in vivo and in vitro t71. We preciously reported various compounds isolated from PsL could inhibit the growth of several human tumor cell lines in vitro E81. In this paper, we report the effects of active

Aloe-emodin (AE) has been demonstrated to have antitumor activity in several tumor cells. However, no information is available on the effect of AE on metastasis in human carcinoma cells. This study was designed to investigate the inhibitory effect of AE on the metastasis potential of HO-8910PM cell line in vitro, and the role of AE in focal adhesion kinase (FAK) expression. Transwell chamber assay was performed to determine the effect of AE on the invasion and migration capacities of the cells. The effect of AE on the adhesion potential of HO-8910PM cells was determined by cell-Matrigel adhesion assay. We found that AE significantly inhibited invasion, migration, and adhesion capacities of HO-8910PM cells, and, furthermore, reduced the protein and mRNA expression of FAK. These findings suggest that the possible mechanistic explanation for the inhibitory effect of AE on metastasis potential in vitro is involved in FAK expression.

To study the skeletal effects of continual and terminated use of risedronate treatment on cortical bone in ovariectomized (Ovx) rats, we used risedronate (Ris), 5 microg x kg(-1), by subcutaneous injections, twice per week. The middle part of the tibial shafts (Tx) were processed undecalcified for quantitive bone histomorphometry. Cortical bone and the marrow areas of the tibial shaft did not change in either sham-Ovx or Ovx rats during the 150-day experimental period. Continued administration of Ris for 150 days decreased the marrow area and increased the percentage of cortical area compared with the matching sham and Ovx group. A decrease in bone formation indices in both periosteal and endocortical surfaces of Tx in sham-operated rats between the age of 5 and 8 months was seen. Ovariectomy increased the percentage of labeled perimeter in the periosteal area, and markedly increased the percentage of eroded perimeter in the endocortical surface compared with sham control groups in 81 and 150 days. Bone formation indices of Ris treatment were increased in periosteal surfaces, and percentages of eroded perimeter were decreased more in endocortical surfaces in 150 days than in the matching sham and Ovx groups. These data matched our static data, which showed a significantly increased percentage of cortical bone area and decreased percentage of marrow area. These bone gains were not maintained in the 90-day Ris withdrawal group. For cancellous bone, the 60-day Ris-treated high bone mass was maintained in the withdrawal group and not maintained in Ris continmuously treated group. These results indicate the effects of constant and terminated use of Ris in cortical bone were different from those in trabecular bone in the proximal tibial metaphysis.