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Aim:To investigate the apoptosis-inducing effect of oridonin,a diterpenoid iso-lated from Rabdosia rubescens,in the human cervical carcinoma HeLa cell line.Methods:A morphological analysis,nuclear condensation,and fragmentation ofchromatin were monitored using Hoechst 33342 staining.Cell viability was as-sessed using the 3-(4,5-dimethylthiazol-(2)-yl)-2,5-diphenyl tetrazolium bromide(MTT) assay.Cell apoptosis and the apoptosis-related activation in the HeLa cellline were evaluated by flow cytometry and Western blotting.Results:Oridoninsuppressed the proliferation of the HeLa cell line in a dose-and time-dependentfashion.Oridonin treatment downregulated the activation of protein kinase B(Akt),the expression of forkhead box class O (FOXO) transcription factor,andglycogen synthase kinase 3 (GSK3).Oridonin also induced the release of cyto-chrome c accompanied by the activation of caspase-3 and poly-adenosine diphos-phate-ribose polymerase cleavage.In addition,Z-D(OMe)-E(OMe)-V-D(OMe)-FMK (z-DEVD-fmk),an inhibitor of caspases,prevented caspase-3 activation andabrogated oridonin-induced cell death.Finally,oridonin treatment of the HeLa cellline downregulated the expression of the inhibitor of the apoptosis protein.Conclusion:Our results showed that oridonin-induced apoptosis involved sev-eral molecular pathways.Oridonin may suppress constitutively activated targetsof phosphatidylinositol 3-kinase (Akt,FOXO,and GSK3) in the HeLa cell line,inhibiting the proliferation and induction of caspase-dependent apoptosis.
Aim: To investigate the apoptosis-inducing effect of oridonin, a diterpenoid iso-lated from Rabdosia rubescens, in the human cervical carcinoma HeLa cell line. Methods: A morphological analysis, nuclear condensation, and fragmentation of chromatin were monitored using Hoechst 33342 staining. Cell viability was as-sessed using the 3- (4,5-dimethylthiazol- (2) -yl) -2,5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and the apoptosis- related activation in the HeLa cell line were evaluated by flow cytometry and Western blotting. Results: Oridoninsuppressed the proliferation of the HeLa cell line in a dose-and time-dependent fashion. Oridonin treatment downregulated the activation of protein kinase B (Akt), the expression of forkhead box class O (FOXO) transcription factor , andglycogen synthase kinase 3 (GSK3). Oridonin also induced the release of cyto-chrome c accompanied by the activation of caspase-3 and poly-adenosine diphos-phate-ribose polymerase cleavage.In addition, ZD (OMe) ) -VD (OMe) -FMK ( z-DEVD-fmk), an inhibitor of caspases, prevented caspase-3 activation and abrogated or idonin-induced cell death. Finaally, oridonin treatment of the HeLa cellline downregulated the expression of the inhibitor of the apoptosis protein. Contact: Our results showed that oridonin -induced apoptosis involved sev-eral molecular pathways. Oridonin may suppress constitutively activated targets of phosphatidylinositol 3-kinase (Akt, FOXO, and GSK3) in the HeLa cell line, inhibiting the proliferation and induction of caspase-dependent apoptosis.