| This paper reports the primary in vitro anticancer activity ofβ-elemene derivates detected using a panel of cultured human tumor cell lines, and focuses on the study of the anticancer activity of XLY19, one of effective derivates, in vitro and in vivo. The mechanism of XLY19 is also investigated.To assess the anti-proliferation effect ofβ-elemene derivates, experiments with SRB staining method were performed in vitro. The results express that majority of these derivates inhibited the proliferation of human promyelocytic leukemia HL-60, human cervical Hela and human gastric adenocarcinoma SGC-7901 cells. Their 50% inhibitive concentrations (IC50s) are lower toβ-elemene. In order to evaluate the potential of being an anticancer drug, three individual experiments as well as the study of toxic effect of normal mice bone marrow cells was conducted. These results demonstrate that XLY19, XLY98, XLY2, XLY6, XLY49 and XLY57 are worth to be further developed.Following, we studied on the in vivo and in vitro anti-tumor effect of XLY19. In vivo, the tumor growth of mice with H22 was inhibited compared with the c6ntrol group after animals were treated with XLY19 i.p. at 25, 50, 100mg·kg-1d-1 for 7 days, and the average tumor suppression rates (3times) of XLY19 at the three doses were respectively 25.30%, 40.85% and 52.15%. The tumor growth of mice with S180was inhibited also, and the average tumor suppression rates (2 times) of it at the three doses was 18.72%,35.53% and 55.94%, respectively. In vitro, the studies demonstrate that XLY19 inhibited the proliferation of HL-60, Hela, SGC-7901, human hepatoma BEL-7402 and human hepatoma HepG2 cells in a dose- and time-dependent manner, SRB assay. The IC50 of XLY19 in the five tumor cell lines were 16.36±0.59,23.21±2.11,26.73±3.82,41.15±1.21,32.27±3.21μmol·L-1.In the study of normal mice lymphocyte proliferation, XLY19 promote it at the doses lower to 7.5μmol·L-1, but reduce it at the doses upper to 15μmol·L-1 in a dose-dependent manner, MTT assay. The study of the clearance of charcoal particles in tumor-bearing mice, it demonstrate that Phagocytosis index (k) was significant rise (p<0.05) at 50 mg·kg-1·d-1, and it was no significant at 100mg·kg-1d-1 and 25 mg·kg-1d-1 (p>0.05).Moreover, under invert microscope we observed the typical morphological changes of apoptosis cells when incubated with XLY19. This strongly hinted us that XLY19 might exert its anticancer activity through triggering tumor cells apoptosis. So we studied the morphological and biochemical characteristics of tumor cells after treated with XLY19. Optic microscope and fluorescence microscope photomicroscopical observation and DNA agarose gel electrophoresis showed that XLY19 induced cell apoptosis in SGC-7901 and Hela cells. Cell cycle was analyzed by flow cytometer. Conclusion that cell cycle was arrested at G0/G1period, and then the cells were induced apoptosis can be educed.In vitro, the anti-proliferation effect of XLY19 on SGC-7901 and Hela cells inhibited by caspase family inhibitor and caspase-3 inhibitor, and caspase-3 activity up-regulated in cells treated with XLY 19.Above all, we conclude that the anticancer mechanism of XLY19 is belonging to inducing tumor cell apoptosis, and this apoptosis may be related to caspase-3.In conclusion, the present thesis first studied on the anticancer effect of XLY19, which is different fr6mβ-elemene hydroxyl-derivates,β-elemene nitrogenous derivates andβ-elemene metal complex in structure, demostrate that the anticancer mechanism of it is because of inducing tumor cells apoptosis, and deduce it induce cells apoptosis by up-regulation of caspase-3 activity. Our research can be helpful to the development of XLY 19 to anticancer drug in the future.
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