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Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia-lymphoma cells.

Taniguchi H, Hasegawa H, Sasaki D, Ando K, Sawayama Y, Imanishi D, Taguchi J, Imaizumi Y, Hata T, Tsukasaki K, Uno N, Morinaga Y, Yanagihara K, Miyazaki Y - Cancer Sci. (2014)

Bottom Line: AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin.In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines.Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Hematology, Sasebo City General Hospital, Sasebo, Japan; Atomic Bomb Disease and Hibakusha Medicine Unit, Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

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Growth inhibitory effects of SGI-1776 in adult T-cell leukemia–lymphoma. SGI-1776, a pan-PIM kinase inhibitor, inhibited cellular survival suppression in adult T-cell leukemia–lymphoma-related cell lines in both dose- and cell-dependent manners (a). Furthermore, SGI-1776 inhibited cellular survival in primary adult T-cell leukemia–lymphoma cells (b).
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fig07: Growth inhibitory effects of SGI-1776 in adult T-cell leukemia–lymphoma. SGI-1776, a pan-PIM kinase inhibitor, inhibited cellular survival suppression in adult T-cell leukemia–lymphoma-related cell lines in both dose- and cell-dependent manners (a). Furthermore, SGI-1776 inhibited cellular survival in primary adult T-cell leukemia–lymphoma cells (b).

Mentions: To confirm the importance of PIM kinases in ATL cells, we evaluated the inhibitory effect of SGI-1776 on those, as well as proliferation of ATL-related cell lines and primary ATL cells. When ATL-related cell lines were cultured with various concentrations (0–10 μM) of SGI-1776 for 72 h, cellular proliferation was inhibited in both dose- and cell-dependent manners (Fig. 7a). In primary ATL cells, SGI-1776 at 10 μM inhibited cellular proliferation (Fig. 7b). Together, these results suggest that PIM kinases may be a novel therapeutic target for treatment of ATL.


Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia-lymphoma cells.

Taniguchi H, Hasegawa H, Sasaki D, Ando K, Sawayama Y, Imanishi D, Taguchi J, Imaizumi Y, Hata T, Tsukasaki K, Uno N, Morinaga Y, Yanagihara K, Miyazaki Y - Cancer Sci. (2014)

Growth inhibitory effects of SGI-1776 in adult T-cell leukemia–lymphoma. SGI-1776, a pan-PIM kinase inhibitor, inhibited cellular survival suppression in adult T-cell leukemia–lymphoma-related cell lines in both dose- and cell-dependent manners (a). Furthermore, SGI-1776 inhibited cellular survival in primary adult T-cell leukemia–lymphoma cells (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317953&req=5

fig07: Growth inhibitory effects of SGI-1776 in adult T-cell leukemia–lymphoma. SGI-1776, a pan-PIM kinase inhibitor, inhibited cellular survival suppression in adult T-cell leukemia–lymphoma-related cell lines in both dose- and cell-dependent manners (a). Furthermore, SGI-1776 inhibited cellular survival in primary adult T-cell leukemia–lymphoma cells (b).
Mentions: To confirm the importance of PIM kinases in ATL cells, we evaluated the inhibitory effect of SGI-1776 on those, as well as proliferation of ATL-related cell lines and primary ATL cells. When ATL-related cell lines were cultured with various concentrations (0–10 μM) of SGI-1776 for 72 h, cellular proliferation was inhibited in both dose- and cell-dependent manners (Fig. 7a). In primary ATL cells, SGI-1776 at 10 μM inhibited cellular proliferation (Fig. 7b). Together, these results suggest that PIM kinases may be a novel therapeutic target for treatment of ATL.

Bottom Line: AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin.In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines.Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Hematology, Sasebo City General Hospital, Sasebo, Japan; Atomic Bomb Disease and Hibakusha Medicine Unit, Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

Show MeSH
Related in: MedlinePlus