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Research Paper
NF-κB Does Not Influence the Induction of Apoptosis by Ukrain
Julia Mendoza, Ruben Zamora, Juan C. Gallardo, Gisela Ceballos, Aida Aldana, Magali Espinosa, Vilma Maldonado and Jorge Melendez-Zajgla
volume 5 | issue 7
july 2006Pages: 788-793
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Ukrain is a reaction product of different alkaloids from Chelidonium majus L.
(celandine) conjugated with thiophosphoric acid. It has immunoregulatory effects on
T lymphocyte subsets and cytotoxic and cytostatic effects on various malignant cells.
Although Ukrain has been reported to induce alterations in the cell cycle and tubulin
polymerization, the specific cellular target has not been described. Since
antineoplasic agents induce NF-κB and their effects are regulated by this
transcription factor, we investigated its possible participation in the apoptotic effects
of Ukrain.
Ukrain induced apoptosis in a panel of cancer cell lines by activating the
intrinsic cell death pathway, as demonstrated by the cleavage of caspase 9 and the
up-regulation and cleavage of caspase 3. The effect was reversible, since long
exposures (24 hours or more) were needed, as verified by clonogenic assays. Gene
reporter assays showed that Ukrain activated NF-κB. Nevertheless, this
activation was not required for, and did not modulate, the Ukrain effect: neither
blockage of activation by a dominant negative version of Iκ-Bα or a Bcl-3
siRNA, nor activation of the pathway by over-expression of IKK2, changed the
response to the drug.
In conclusion, Ukrain induced apoptosis in HeLa cervical cancer cells by
activating the intrinsic pathway. In contrast to other antineoplasic drugs, the effects of
Ukrain were not regulated by NF-κB.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.