Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 100956087 Publication Model: Print Cited Medium: Print ISSN: 1671-4083 (Print) Linking ISSN: 16714083 NLM ISO Abbreviation: Acta Pharmacol Sin Subsets: MEDLINE
    • Publication Information:
      Publication: 2009- : New York : Nature Publishing Group
      Original Publication: Beijing, China : Science Press, c2000-
    • Subject Terms:
      Phosphoinositide-3 Kinase Inhibitors*; Apoptosis/*drug effects ; Diterpenes, Kaurane/*pharmacology ; Proto-Oncogene Proteins c-akt/*antagonists & inhibitors ; Uterine Cervical Neoplasms/*pathology; Caspases/metabolism ; Collagen Type XI/metabolism ; Cytochromes c/metabolism ; Down-Regulation/drug effects ; Female ; HeLa Cells ; Humans ; In Vitro Techniques ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/metabolism ; Phosphorylation ; Signal Transduction/drug effects ; Uterine Cervical Neoplasms/drug therapy
    • Abstract:
      Aim: To investigate the apoptosis-inducing effect of oridonin, a diterpenoid isolated 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 assessed 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: Oridonin suppressed 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, and glycogen synthase kinase 3 (GSK3). Oridonin also induced the release of cytochrome c accompanied by the activation of caspase-3 and poly-adenosine diphosphate- 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 and abrogated oridonin-induced cell death. Finally, oridonin treatment of the HeLa cell line downregulated the expression of the inhibitor of the apoptosis protein.
      Conclusion: Our results showed that oridonin-induced apoptosis involved several 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.
    • Accession Number:
      0 (COL11A2 protein, human)
      0 (Collagen Type XI)
      0 (Diterpenes, Kaurane)
      0 (Phosphoinositide-3 Kinase Inhibitors)
      0APJ98UCLQ (oridonin)
      9007-43-6 (Cytochromes c)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 3.4.22.- (Caspases)
    • Publication Date:
      Date Created: 20071026 Date Completed: 20090512 Latest Revision: 20191210
    • Publication Date:
      20221213
    • Accession Number:
      10.1111/j.1745-7254.2007.00667.x
    • Accession Number:
      17959034