ABSTRACT
Objective To evaluate the genetic toxicity of Wentilactone A. Methods The classical genotoxicity test combination (Ames test, in vitro CHO cell chromosome aberration test and mouse bone marrow micronucleus test) was used to detect the genotoxicity of Wentilactone A. Results Ames test suggested that Wentilactone A was not mutagenic against Salmonella typhimurium with or without the metabolic activation system (S9) at five doses of 5 000, 500, 50, 5, and 0.5 μg/dish. CHO cell chromosome aberration test suggested that the CHO cells cultured in 4 h and 24 h did not induce chromosomal aberrations in three dose groups at the final concentration of 23.74, 47.48, 94.96 μg/ml, with and without S9. The mouse bone marrow micronucleus test showed no significant difference in the bone marrow micronucleus induction rate of cells at three doses of 100, 200, and 400 mg/kg treated for 24 h and at dose of 400 mg/kg treated for 48 h compared with the solvent control group (P>0.05). Conclusion These results indicated that Wentilactone A did not exhibit genetic toxicity based on the Ames test, CHO chromosomal aberration test and micronucleus assay. It was suggested that Wentilactone A had no genetic toxicity and potential carcinogenicity.
ABSTRACT
Objective ToinvestigatemechanismofWentilactoneA (WA)inhibitionofsmallcelllungcancer(SCLC)cell line NCI-H1688 migration .Methods The migration and proliferation were analyzed by wounding-healing assay and MTT assay [3-(4 ,5-Dimethylthiazol-2-yl)-2 ,5-diphenyltetrazolium bromide ,MTT] .Immunofluorescence was used to confirm the ex-pression of ATF3 protein after WA treatment .Western blot was used to examine the expression of key proteins in ATF3/Nrf2/AKR1C1 signal pathway .Results WA inhibits the proliferation and migration of SCLC .MTT analysis showed WA in-hibits the proliferation of NCI-H1688 cell line in a time-dependent manner .The number of migrated cells in WA treatment group was (8 .73 ± 1 .06) mm ,which was lower than that of control group (15 .63 ± 3 .11) mm ,The number of migrated cells in AKR1C1 expression group was (24 .37 ± 0 .90) mm ,the number of migrated cells in AKR1C1 expression and WA treatment group was (14 .17 ± 1 .31) mm ,with significant difference (P<0 .05) .WA enhances the nuclear expression of ATF3 ,and then reduces the expression of p-Nrf2 and AKR1C1 .Conclusion WA inhibits the proliferation and migration of SCLC through ATF3/Nrf2/AKR1C1 signal pathway .