TY - JOUR
T1 - NF-κB does not influence the induction of apoptosis by Ukrain
AU - Mendoza, Julia
AU - Zamora, Ruben
AU - Gallardo, Juan C.
AU - Ceballos, Gisela
AU - Aldana, Aida
AU - Espinosa, Magali
AU - Maldonado, Vilma
AU - Melendez-Zajgla, Jorge
PY - 2006/7
Y1 - 2006/7
N2 - 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 upregulation 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-κ B. 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-B a or a Bcl-3 siRNA, nor activation of the pathway by overexpression 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-κ B.
AB - 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 upregulation 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-κ B. 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-B a or a Bcl-3 siRNA, nor activation of the pathway by overexpression 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-κ B.
KW - Apoptosis
KW - Bcl-3
KW - IKK2
KW - IκBα
KW - NF-κB
KW - Ukrain
UR - http://www.scopus.com/inward/record.url?scp=33751187879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751187879&partnerID=8YFLogxK
U2 - 10.4161/cbt.5.7.2752
DO - 10.4161/cbt.5.7.2752
M3 - Article
C2 - 16721042
AN - SCOPUS:33751187879
SN - 1538-4047
VL - 5
SP - 788
EP - 793
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 7
ER -