RT Journal Article
T1 Apoptosis induced by paclitaxel via Bcl-2, Bax and caspases 3 and 9 activation in NB4 human leukaemia cells is not modulated by ERK inhibition
A1 Morales Cano, Daniel
A1 Calviño, Eva
A1 Rubio, Virginia
A1 Herráez, Ángel
A1 Sancho, Pilar
A1 Tejedor, M. Cristina
A1 Díez, José C.
AB We have studied the role of pivotal bio-molecules involved in signalling of cytotoxic effects induced by paclitaxel (Ptx) on acute promyelocytic human leukaemia NB4 cells. A time-dependent increase in cell death and DNA cleavage was observed after 30 μM Ptx treatment. Cell death induction by Ptx proceeds mainly as programmed cell death as shown by annexin V-FITC, reaching up to 30% of apoptotic cells after 24. h. Significant reductions of p53, changes in Bax and Bcl-2 and activation of caspases 3 and 9 were observed as the treatment was applied for long times. Ptx treatments produced NFkB depletion with expression levels abolished at 19. h what could be involved in reduction of survival signals. Phosphorylation of intracellular kinases showed that pERK1/2 decreased significantly at 19. h of Ptx treatment. When these cells were preincubated for 90. min with 20 μM PD98059, 2'-amino-3'-methoxyflavone, an inhibitor of ERK phosphorylation, a slight reduction of cell viability was observed in comparison to that produced by Ptx alone. Pretreatment with PD98059 neither activated caspases nor significantly increased the apoptotic effect of Ptx. Taken together, our data reveal that the inhibition of ERK phosphorylation does not seem to be an essential pathway for bursting an increased induction of apoptosis by Ptx. Decrease of p53 and Bcl-2, fragmentation of DNA, increase of Bax and, finally, activation of caspases 3 and 9 in NB4 leukaemia cells make the apoptotic process induced by Ptx irreversible. Application of Ptx in leukaemia cells shows therefore a promising potential with particular effects on different leukaemia cell types.
PB Elsevier
SN 0940-2993
YR 2013
FD 2013-11
LK https://hdl.handle.net/20.500.14352/98666
UL https://hdl.handle.net/20.500.14352/98666
LA eng
NO Morales-Cano D, Calviño E, Rubio V, Herráez A, Sancho P, Tejedor MC, Diez JC. Apoptosis induced by paclitaxel via Bcl-2, Bax and caspases 3 and 9 activation in NB4 human leukaemia cells is not modulated by ERK inhibition. Exp Toxicol Pathol. 2013 Nov;65(7-8):1101-8. doi: 10.1016/j.etp.2013.04.006. Epub 2013 Jun 2. PMID: 23735541.
DS Docta Complutense
RD 21 abr 2025