Phorbol ester (12-O-tetradecanoylphorbol 13-acetate) prevents ornithine decarboxylase inhibition and apoptosis in L1210 leukemic cells exposed to TGF-β1

Motyl, T.; Kasterka, M.; Grzelkowska, K.; Ostrowski, Jerzy; Filipecki, Marcin; Malicka, E.; Pioszaj, T.

doi:10.1016/s1357-2725(96)00083-0

Cited by 13 publications

(5 citation statements)

References 33 publications

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“…Data exist that both cisplatin (Chu, 1994) and TGF b1 (Heldin et al, 1997;Massague, 1998) can induce apoptosis in tumor cells, including cisplatin-sensitive L1210 cells (Motyl et al, 1996). Here we show that TGF b1 in concentration of 5 ng/ml is ineffective in the induction of apoptosis in cisplatin-resistant L1210 cells (Fig.…”

Section: Apoptosis Of Cisplatin-sensitive and Cisplatin-resistant L12supporting

confidence: 48%

“…i, P < 0.05 (L1210/S versus L1210/R cells). L1210/S cells (Motyl et al, 1996;Stoika et al, 1999;Yakymovych et al, 1999). We also studied the expression of phosphorylated Smad 2 because it is known that such modification is necessary for realization of its signal transduction function (Heldin et al, 1997;Massague, 1998;Souchelnytskyi, 2002).…”

Section: Expression Of Different Smad Proteins In Cisplatin-sensitivementioning

confidence: 99%

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Potential role of transforming growth factor beta1 in drug resistance of tumor cells.

Stoika

Yakymovych²,

Souchelnytskyi³

et al. 2003

Acta Biochim Pol

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Acquired drug resistance of tumor cells is frequently observed in cancer patients undergoing chemotherapy. We studied murine leukemia L1210 cells sensitive and resistant to the cytotoxic action of cisplatin and showed that cisplatin-resistant leukemia cells were also refractory to TGF beta1-dependent growth inhibition and apoptosis. Addressing the question about the mechanisms responsible for the cross-resistance to cisplatin and TGF beta1, we found that cisplatin- and TGF beta1-resistant L1210 cells possessed a decreased expression of type I TGF beta1 receptor, while the expression of type II TGF beta1 receptor was not affected. Western blot analysis of Smad proteins 2, 3, 4, 6, and 7, which participate in signal transduction pathway down-stream of the TGF beta1 receptors, revealed an increased expression of Smad 6, inhibiting TGF beta1 action, only in cisplatin- and TGF beta1-resistant L1210 cells. TGF beta1 and especially the cytotoxic mistletoe agglutinin increased Smad 6 expression in TGF beta1-sensitive but not in TGF beta1-resistant L1210 cells. TGF beta1-resistant L1210 cells also differed from TGF beta1-sensitive cells by the lack of expression of the pro-apoptotic p53 protein and higher level of expression of the anti-apoptotic Bcl-2 protein. Thus, the described co-expression of tumor cell refractoriness to an anti-cancer drug and to the inhibitory cytokine TGF beta1 is accompanied by multiple changes in the TGF beta1 signal transduction pathway and in other regulatory systems of the target cells. Besides, we found that various anti-tumor drugs and cytotoxic plant lectins increased the level of TGF beta1 expression in both TGFbeta1-sensitive and -resistant L1210 cells. A hypothesis is proposed that TGFbeta1 can at least partly mediate the effect of cell-stressing agents and, thus, the development of TGF beta1 resistance may be responsible for the appearance of tumor cell refractoriness to the action of some anti-cancer drugs.

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Section: Apoptosis Of Cisplatin-sensitive and Cisplatin-resistant L12supporting

confidence: 48%

Section: Expression Of Different Smad Proteins In Cisplatin-sensitivementioning

confidence: 99%

Potential role of transforming growth factor beta1 in drug resistance of tumor cells.

Stoika

Yakymovych²,

Souchelnytskyi³

et al. 2003

Acta Biochim Pol

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“…In addition, previous studies suggested that ODC could represent a downstream element of PKC-mediated mitogenic signalling [29][30][31], and might be involved in tumour cell invasion in vitro [32][33][34][35]. These data raised the possibility that ODC also played a role in the abovementioned actions of PKC on the invasiveness of the glioma cell lines.…”

Section: Involvement Of Odc In Pkc-mediated Mt1-mmp Expression Mmp-2mentioning

confidence: 88%

“…Available in vitro data suggest an involvement of mitogen-activated protein kinase/extracellular-signal-regulated kinase 1 (MEK-1) and ODC in the stimulatory effects of PKC on tumour cell proliferation [29][30][31], while ODC and extracellular-signal-regulated kinases 1 and/or 2 (ERK1/2) have been implicated in tumour cell invasion [32][33][34][35][36][37][38]. Therefore, we also asked whether these enzyme systems were involved in the actions of PKC on the invasiveness of the glioma cell lines.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase C-Mediated in vitro Invasion of Human Glioma Cells through Extracellular-Signal-Regulated Kinase and Ornithine Decarboxylase

et al. 2000

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We investigated the involvement of protein kinase C (PKC) in the in vitro invasiveness of the A-172, U-87 and U-373 human glioma cell lines, as well as the role of ornithine decarboxylase (ODC) and/or extracellular-signal-regulated kinase (ERK) in the actions of PKC. Thus, cells were treated under serum-free conditions with the PKC activator phorbol 12-myristate 13-acetate (PMA), or with the PKC inhibitors bisindolylmaleimide I (GF 109203X) or calphostin C in the absence or presence of the ODC inhibitor D,L-α-difluoromethylornithine (DFMO), and/or the mitogen-activated protein kinase/extracellular-signal-regulated kinase inhibitor 2′-amino-3′-methoxyflavone (PD 098059). Subsequently, cells were assessed for membrane-type 1 matrix metalloproteinase (MT1-MMP) mRNA contents, 72-kD latent, and 59/62-kD activated matrix metalloproteinase 2 (MMP-2) in conditioned media, as well as invasiveness. For these purposes, we used Northern blot analysis, gelatine zymography, and an in vitro filter invasion assay, respectively. Data were related to those found with untreated cells. PKC activity was 2- to 3-fold stimulated by PMA (100 nM for 30 min), and about 2-fold inhibited by calphostin C (40 nM for 2 h) or GF 109203X (5 µM for 20 min). This was accompanied by a similar increase or decrease, respectively, in MT1-MMP mRNA expression, 59/62-kD MMP-2 activity, and in vitro invasion. Inhibition of ODC activity (about 2-fold by 24 h DFMO 5 mM), ERK activation (almost completely by 20 min PD 098059 50 µM), or both these enzymes simultaneously led to a reduction by about half in levels of MT1-MMP mRNA, 59/62-kD MMP-2 activity, and invasion in untreated as well as PMA-stimulated cells. The use of these compounds did not significantly alter the inhibitory effects of GF 109203X or calphostin C. Modulation of PKC and/or ERK activity resulted in corresponding changes in ERK and/or ODC activities, but interference with ODC affected neither ERK nor PKC. Our data suggest a regulatory role for PKC, in co-operation with ERK and ODC, in glioma cell invasion, by modulation of MT1-MMP mRNA expression and MMP-2 activation.

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“…Our previous investigations [25,51] demonstrated that L1210 leukaemic cells are "primed" to apoptosis and could serve as a convenient object to study the mechanisms of programmed cell death. The objective of this study was to explore the effect of TNF-α and/or quercetin on survival and/or apoptosis of L1210 cells.…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis and NF-$\kappa$B by quercetin in growing murine L1210 lymphocytic leukaemic cells potentiated by TNF-$\alpha$

et al. 2000

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-Polyphenol quercetin induced apoptosis in proliferating murine L1210 lymphocytic cells. DNA damage, as well as apoptosis and withdrawal from the cell cycle were transient. The above mentioned death promoting activity of quercetin was enhanced by physiological concentrations of TNF-α. At the same time, indices of cell viability dropped. However, the extent and tendency of the initially enhanced cell mortality steadily diminished throughout the experiment. After 12 h the G2/M phase reappeared. After 24 h all indices almost returned to control levels indicating either the selection of subpopulation of unaffected leukaemic cells or cells developing resistance to the treatment. A DNA ladder of oligonucleosomes was observed for apoptogenic treatments. We conclude that quercetin unmasked cell death, promoting the activity of TNF-α. However, after 12 and 24 h of exposure, surviving cells could complete the cell cycle and finally recover. At the same time, increased NF-κB activation was demonstrated by immunoblotting of the immunoreactive RelA/p65 subunit in nuclear extracts. Exposure to TNF-α or quercetin was crucial for increased activity of NF-κB, which may implicate an increasing resistance to their cytotoxicity. quercetin / TNF-α / leukaemia / apoptosis / NF-κB Reprod. Nutr. Dev. 40 (2000) 441

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Phorbol ester (12-O-tetradecanoylphorbol 13-acetate) prevents ornithine decarboxylase inhibition and apoptosis in L1210 leukemic cells exposed to TGF-β1

Cited by 13 publications

References 33 publications

Potential role of transforming growth factor beta1 in drug resistance of tumor cells.

Potential role of transforming growth factor beta1 in drug resistance of tumor cells.

Protein Kinase C-Mediated in vitro Invasion of Human Glioma Cells through Extracellular-Signal-Regulated Kinase and Ornithine Decarboxylase

Induction of apoptosis and NF-$\kappa$B by quercetin in growing murine L1210 lymphocytic leukaemic cells potentiated by TNF-$\alpha$

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