β-Elemene inhibits Hsp90/Raf-1 molecular complex inducing apoptosis of glioblastoma cells
BACKGROUND & OBJECTIVE Elemene, isolated from the Chinese medicinal herb Rhizoma Zedoariae, was shown to exhibit antitumor activity. Our previous studies showed that elemene had a markedly antineoplastic activity on glioma. This study was designed to investigate the proliferation inhibitory effect and the apoptosis-inducing activity of elemene on glioma cells. METHODS The effects of elemene on cell proliferation were studied in vitro by using (3)H-TdR incorporation. The morphological alterations were confirmed by Hoechst 33258/PI staining. The apoptosis was evaluated by flow cytometry analysis and agarose gel electrophoresis. RESULTS Elemene exhibited a marked antiproliferative effect on rat glioma cell C6 and human glioma cell SHG-44. The fifty percent inhibition concentration (IC(50)) of elemene against glioma cell lines at different time points (D1-D4) by (3)H-TdR incorporation was C6 7.33-11.02 mg/L, SHG-44 13.29-27.16 mg/L. At the same concentration, human glioma cell line SHG-44 was found to be less sensitive to elemene compared to rodent cell line C6. The characteristic nucleolus alternations under fluorescent microscope included condensation of chromatin arranged under the nuclear membrane and apoptotic bodies, with a low nuclear/cytoplasmic ratio. In flow cytometry analysis, a typical subdiploid peak before Phase G(0)/G(1) (apoptotic peak) was detected in DNA frequency distribution histograms. Also the apoptosis in glioma cells was confirmed by DNA ladder formation on gel electrophoresis. CONCLUSION Elemene exhibited a marked antiproliferative effect on glioma cells, and it could induce apoptosis in vitro.