Tyrosine kinase inhibitor-induced differentiation of K-562 cells: alterations of cell cycle and cell surface phenotype

Hunáková, Ľuba; Sedlák, J; Klobusická, M; Duraj, J; Chorváth, B

doi:10.1016/0304-3835(94)90168-6

Cited by 19 publications

(5 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, HEL and MEG‐01 cells may require pathways other than K562 to produce adhesion. In support of this notion, these cell lines were shown to have distinct expression patterns for proteins involved in cell adhesion [21,22]. Furthermore, a differential inhibitory effect of α‐ and β‐tocopherol on cell adhesion of K562 and HEL cells has been observed [23].…”

Section: Discussionmentioning

confidence: 72%

Disabled‐2 small interfering RNA modulates cellular adhesive function and MAPK activity during megakaryocytic differentiation of K562 cells

Tseng

Huang

et al. 2003

FEBS Letters

View full text Add to dashboard Cite

Previous studies have shown that Disabled-2 (DAB2) is up-regulated during megakaryocytic di¡erentiation of human K562 cells. To delineate the consequences of DAB2 induction, a DNA vector-based small interfering RNA (siRNA) was designed to intervene in DAB2 expression. We found that DAB2 siRNA speci¢cally inhibited DAB2 induction, resulting in the modulation of cell^cell adhesion and mitogen-activated protein kinase (MAPK) phosphorylation. The morphological changes and L L3 integrin expression associated with megakaryocytic differentiation were not a¡ected. Since the MAPK pathway has been shown to involve DAB2 induction [Tseng et al., Biochem. Biophys. Res. Commun. 285 (2001) 129^135], our results suggest a reciprocal regulation between DAB2 and MAPK in the di¡erentiation of K562 cells. In addition, we have demonstrated for the ¢rst time that DAB2 siRNA is a valuable tool for unveiling the biological consequences of DAB2 expression.

show abstract

Section: Discussionmentioning

confidence: 72%

Disabled‐2 small interfering RNA modulates cellular adhesive function and MAPK activity during megakaryocytic differentiation of K562 cells

Tseng

Huang

et al. 2003

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…38 Induction of cellular differentiation by vitamin D 3 and analogues, as well as the tyrosine kinase inhibitor herbicmycin A are also associated with G 1 arrest. 39,40 Exposure to the polar planar differentiation inducer HMBA causes a number of potentially important metabolic events which lead to cell cycle arrest. These include down-regulation of p107, cdk4, and accumulation of underphosphorylated RB and p130, [41][42][43] associated with prolongation of G 1 .…”

Section: Discussionmentioning

confidence: 99%

Phenylbutyrate-induced G1 arrest and apoptosis in myeloid leukemia cells: structure–function analysis

et al. 1999

Leukemia

View full text Add to dashboard Cite

The aromatic fatty acid phenylbutyrate (PB) induces cytostasis, differentiation, and apoptosis in primary myeloid leukemic cells at clinically achievable concentrations. In the present study, we have investigated the structural and cellular basis for PBinduced cytostasis, using the ML-1 human myeloid leukemia cell line as a model system. PB induced a dose-dependent increase in cells in G1 with a corresponding decrease in cells in S-phase of the cell cycle. At comparable doses, PB induced expression of CD11b, indicating myeloid differentiation. At higher doses, the drug induced apoptosis. The antitumor activity was independent of the aromatic ring, as butyric acid (BA) was of equal or greater potency at producing these biological changes. In contrast, shortening of the fatty acid carbon chain length, as demonstrated with phenylacetate (PA), significantly diminished drug potency. Consistent with their effects on cell cycle, PB and BA, but not PA, induced the cyclindependent kinase inhibitor, p21 WAF1/CIP1 , and led to the appearance of hypophosphorylated Rb, suggesting a role for p21 WAF1/CIP1 in PB-induced cytostasis. Therefore, it appears that the fatty acid moiety of PB, rather than its aromatic ring, is critical for its activity in myeloid leukemic cells. These data provide a potential mechanistic basis for the increased potency of PB over PA previously demonstrated in primary leukemic samples, and support the further clinical development of PB in the treatment of hematologic malignancies.

show abstract

“…38 Induction of cellular differentiation by vit-amin D 3 and analogues, as well as the tyrosine kinase inhibitor herbicmycin A are also associated with G 1 arrest. 39,40 Exposure to the polar planar differentiation inducer HMBA causes a number of potentially important metabolic events which lead to cell cycle arrest. These include down-regulation of p107, cdk4, and accumulation of underphosphorylated RB and p130, [41][42][43] associated with prolongation of G 1 .…”

Section: Discussionmentioning

confidence: 99%

True

1999

Leukemia

View full text Add to dashboard Cite

The aromatic fatty acid phenylbutyrate (PB) induces cytostasis, differentiation, and apoptosis in primary myeloid leukemic cells at clinically achievable concentrations. In the present study, we have investigated the structural and cellular basis for PB-induced cytostasis, using the ML-1 human myeloid leukemia cell line as a model system. PB induced a dose-dependent increase in cells in G1 with a corresponding decrease in cells in S-phase of the cell cycle. At comparable doses, PB induced expression of CD11b, indicating myeloid differentiation. At higher doses, the drug induced apoptosis. The antitumor activity was independent of the aromatic ring, as butyric acid (BA) was of equal or greater potency at producing these biological changes. In contrast, shortening of the fatty acid carbon chain length, as demonstrated with phenylacetate (PA), significantly diminished drug potency. Consistent with their effects on cell cycle, PB and BA, but not PA, induced the cyclin-dependent kinase inhibitor, p21(WAF1/CIP1), and led to the appearance of hypophosphorylated Rb, suggesting a role for p21(WAF1/CIP1) in PB-induced cytostasis. Therefore, it appears that the fatty acid moiety of PB, rather than its aromatic ring, is critical for its activity in myeloid leukemic cells. These data provide a potential mechanistic basis for the increased potency of PB over PA previously demonstrated in primary leukemic samples, and support the further clinical development of PB in the treatment of hematologic malignancies.

show abstract

Tyrosine kinase inhibitor-induced differentiation of K-562 cells: alterations of cell cycle and cell surface phenotype

Cited by 19 publications

References 14 publications

Disabled‐2 small interfering RNA modulates cellular adhesive function and MAPK activity during megakaryocytic differentiation of K562 cells

Disabled‐2 small interfering RNA modulates cellular adhesive function and MAPK activity during megakaryocytic differentiation of K562 cells

Phenylbutyrate-induced G1 arrest and apoptosis in myeloid leukemia cells: structure–function analysis

True

Contact Info

Product

Resources

About