Characterization of salvicine-resistant lung adenocarcinoma A549/SAL cell line.

Salvicine is a diterpenoid quinone derived from a traditional Chinese medication that has been shown to possess potent in vitro and in vivo antitumor effects. This compound, which inhibits the activity of Topoisomerase II, was found to equipotently kill various multidrug-resistant tumor cells and their corresponding parental counterparts in vitro and to inhibit mdr1/P-gp expression in multidrug-resistant K562/A02 cells. To examine the features of tumor resistance to salvicine, we established a salvicine-resistant tumor cell subline of A549 lung adenocarcinoma cells. Compared with parental cells, A549/SAL cells displayed 8.91-fold resistance to salvicine and an average of 6.70-fold resistance to the antimetabolites. A549/SAL cells, however, were not resistant to alkylating agents, platinum compounds and other naturally-derived antineoplastics. RT-PCR analysis showed that the expression of mRNAs from the mdr-1, MRP, PCNA, topoisomerase II alpha and beta, GSTpi, p21 and GADD45 genes was not altered in the salvicine-resistant subline. In contrast, expression of p53 and bax mRNA was significantly lower, and expression of mdm2 mRNA was significantly higher, in A549/SAL cells compared to A549 cells. A549/SAL cells grew more slowly, and in a more scattered pattern, than A549 cells. In addition, the A549/SAL cells showed enhanced ability to migrate and invade in comparison to the parental cells. These results indicate that exposure to salvicine does not induce a tumor multidrug-resistant phenotype.

[Inhibition of mixture of lucid garoderma and lucid garoderma spore on tumor cell in vitro and in vivo].

BACKGROUND & OBJECTIVE: Garoderma lucidum (lingzhi) is a kind of medicinal fungus with a long history in China as a valuable tonic folk remedy. It has been demonstrated that lingzhi had growth inhibition effect against implanted mice tumors. It is generally regarded that anti-tumor action of lingzhi is induced by promoting function of immune system. Recently, we found that mixture of lucid garoderma and lucid garoderma spore (MLGLGS) could markedly inhibit activities of topoisomerase I and II, so this study was designed to further evaluate the inhibition effects of MLGLGS on tumor cell in vitro and in vivo. METHODS: Inhibition of MLGLGS on tumor cell were detected by MTT or SRB method in vitro study and by human tumor nude mice xenografts as models in vivo study. RESULTS: Among them, the IC50 values were lower than 2 mg/ml in P388, U-937, and HL-60 leukemias, and lower than 4 mg/ml in 2 human lung cancer and 2 human gastric cancer cells, respectively. In vivo study revealed that MLGLGS had certain experimental therapeutic action on human lung tumor xenograft LAX-83 (dose: 1 g/kg, inhibitory rate: 49.47%) and gastric xenograft SGC-7901 (dose: 2 g/kg, inhibitory rate: 43.09%). CONCLUSION: MLGLGS has inhibitory action on tumor cell at high concentration and high dosage.

Synthesis and cytotoxicity of dihydroartemisinin ethers containing cyanoarylmethyl group.

A new type of ether of dihydroartemisinin containing cyano and aryl groups was prepared and tested for cytotoxicity to A549, P388, L1210 and HT29 cells using the MTT assay. 12k and 12l were the most cytotoxic compounds. 13 lacking the peroxy group showed a 1000-fold less potency than 12l. Similarly, the inactive compound 14 indicated that the position of cyano groups was also important. Flow cytometry data showed that the compounds caused an accumulation of P388 cells in the G(1)-phase of the cell cycle.