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. 2008 Sep;22(9):1803-6.
doi: 10.1038/leu.2008.196. Epub 2008 Jul 31.

Rac guanosine triphosphatases represent a potential target in AML

L U W Müller, R J Schore, Y Zheng, E K Thomas, M-O Kim, J A Cancelas, Y Gu, D A Williams

Rac guanosine triphosphatases represent a potential target in AML

L U W Müller et al. Leukemia. 2008 Sep.
No abstract available

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Figures

Figure 1
Figure 1
The Rac-specific inhibitor NSC23766 significantly impacts proliferation, survival, and cell cycle progression of human AML cell lines. (A) Proliferation of a panel of AML cell lines was analyzed by MTS assay 72 hrs after exposure to increasing doses of NSC23766 (n=3, 24 wells per condition). Black bars indicate 0 µM, hatched bars 20 µM, and white bars 40 µM NSC23766. (B) NSC23766 inhibits Rac activation in ML-2 cells. ML-2 cells were cultured in the presence of increasing doses of NSC23766. Lysates were analyzed for active, GTP-Rac. As controls, total lysates were analyzed for Rac and actin expression. (C) Apoptosis of ML-2 and CD34+ cells was analyzed 72 hours after exposure to NSC23766. Left panel depicts a representative dot blot analysis. Numbers indicate percentage of cells per quadrant. Graph depicts percentage of 7AAD-positive cells after exposure to 0 µM (black bars), 20 µM (hatched bars), or 40 µM (white bars) NSC23766 (n=5). (D) Cell cycle analysis of ML-2 and CD34+ cells was performed 48 hours after exposure to NSC23766. Left panel depicts representative dot blot after exposure to 0 or 40 µM NSC23766. Graph depicts percentage of cells in G1/G0 or S phase of cell cycle 48 hours after exposure to 0 µM (black bars) or 40 µM (white bars) NSC23766, respectively (n=5). ** p<0.01, NS = not significant.
Figure 1
Figure 1
The Rac-specific inhibitor NSC23766 significantly impacts proliferation, survival, and cell cycle progression of human AML cell lines. (A) Proliferation of a panel of AML cell lines was analyzed by MTS assay 72 hrs after exposure to increasing doses of NSC23766 (n=3, 24 wells per condition). Black bars indicate 0 µM, hatched bars 20 µM, and white bars 40 µM NSC23766. (B) NSC23766 inhibits Rac activation in ML-2 cells. ML-2 cells were cultured in the presence of increasing doses of NSC23766. Lysates were analyzed for active, GTP-Rac. As controls, total lysates were analyzed for Rac and actin expression. (C) Apoptosis of ML-2 and CD34+ cells was analyzed 72 hours after exposure to NSC23766. Left panel depicts a representative dot blot analysis. Numbers indicate percentage of cells per quadrant. Graph depicts percentage of 7AAD-positive cells after exposure to 0 µM (black bars), 20 µM (hatched bars), or 40 µM (white bars) NSC23766 (n=5). (D) Cell cycle analysis of ML-2 and CD34+ cells was performed 48 hours after exposure to NSC23766. Left panel depicts representative dot blot after exposure to 0 or 40 µM NSC23766. Graph depicts percentage of cells in G1/G0 or S phase of cell cycle 48 hours after exposure to 0 µM (black bars) or 40 µM (white bars) NSC23766, respectively (n=5). ** p<0.01, NS = not significant.
Figure 1
Figure 1
The Rac-specific inhibitor NSC23766 significantly impacts proliferation, survival, and cell cycle progression of human AML cell lines. (A) Proliferation of a panel of AML cell lines was analyzed by MTS assay 72 hrs after exposure to increasing doses of NSC23766 (n=3, 24 wells per condition). Black bars indicate 0 µM, hatched bars 20 µM, and white bars 40 µM NSC23766. (B) NSC23766 inhibits Rac activation in ML-2 cells. ML-2 cells were cultured in the presence of increasing doses of NSC23766. Lysates were analyzed for active, GTP-Rac. As controls, total lysates were analyzed for Rac and actin expression. (C) Apoptosis of ML-2 and CD34+ cells was analyzed 72 hours after exposure to NSC23766. Left panel depicts a representative dot blot analysis. Numbers indicate percentage of cells per quadrant. Graph depicts percentage of 7AAD-positive cells after exposure to 0 µM (black bars), 20 µM (hatched bars), or 40 µM (white bars) NSC23766 (n=5). (D) Cell cycle analysis of ML-2 and CD34+ cells was performed 48 hours after exposure to NSC23766. Left panel depicts representative dot blot after exposure to 0 or 40 µM NSC23766. Graph depicts percentage of cells in G1/G0 or S phase of cell cycle 48 hours after exposure to 0 µM (black bars) or 40 µM (white bars) NSC23766, respectively (n=5). ** p<0.01, NS = not significant.
Figure 2
Figure 2
NSC23766 significantly delays the development of leukemia in a murine in vivo model. 2 × 107 ML-2 cells were transplanted into sublethally irradiated NOD/SCID mice. Arrows indicate placement/removal of Alzet osmotic pumps containing PBS (solid line, n=8) or NSC23766 (dotted line, n=9). ** p < 0.01 (log-rank test).
See this image and copyright information in PMC

References

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