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Heat shock protein 90 inhibitors repress latent membrane protein 1 (LMP1) expression and proliferation of Epstein-Barr virus-positive natural killer cell lymphoma.

Murata T, Iwata S, Siddiquey MN, Kanazawa T, Goshima F, Kawashima D, Kimura H, Tsurumi T - PLoS ONE (2013)

Bottom Line: We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells.Tumor formation in immuno-defficient NOD/Shi-scid/IL-2Rγ() (NOG) mice was also retarded.These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.

View Article: PubMed Central - PubMed

Affiliation: Division of Virology, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.

ABSTRACT
Epstein-Barr virus (EBV) LMP1 is a major oncoprotein expressed in latent infection. It functions as a TNFR family member and constitutively activates cellular signals, such as NFκB, MAPK, JAK/STAT and AKT. We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells. Tumor formation in immuno-defficient NOD/Shi-scid/IL-2Rγ() (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.

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HSP90 inhibitors suppress cell proliferation of the EBV-positive SNK6 NK lymphoma line.SNK6 cells were cultured with Radicicol (A) or 17-AAG (B) at concentrations of 3, 1, 0.3 or 0.1 µM and cell numbers were counted on days 0, 2 and 4. Data are shown as the means of three independent replicates.
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pone-0063566-g003: HSP90 inhibitors suppress cell proliferation of the EBV-positive SNK6 NK lymphoma line.SNK6 cells were cultured with Radicicol (A) or 17-AAG (B) at concentrations of 3, 1, 0.3 or 0.1 µM and cell numbers were counted on days 0, 2 and 4. Data are shown as the means of three independent replicates.

Mentions: After confirming that HSP90 inhibitors repress LMP1 expression in EBV-positive lymphoma cells, we then examined whether the inhibitors might actually suppress cancerous growth. We first tested at the cell culture level (Fig. 3). Three or 1 µM of Radicicol (Fig. 3A) or 17-AAG (Fig. 3B) could fully block proliferation of SNK6 cells depending on the concentration. Partial but appreciable inhibition was also exhibited at lower concentrations.


Heat shock protein 90 inhibitors repress latent membrane protein 1 (LMP1) expression and proliferation of Epstein-Barr virus-positive natural killer cell lymphoma.

Murata T, Iwata S, Siddiquey MN, Kanazawa T, Goshima F, Kawashima D, Kimura H, Tsurumi T - PLoS ONE (2013)

HSP90 inhibitors suppress cell proliferation of the EBV-positive SNK6 NK lymphoma line.SNK6 cells were cultured with Radicicol (A) or 17-AAG (B) at concentrations of 3, 1, 0.3 or 0.1 µM and cell numbers were counted on days 0, 2 and 4. Data are shown as the means of three independent replicates.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643901&req=5

pone-0063566-g003: HSP90 inhibitors suppress cell proliferation of the EBV-positive SNK6 NK lymphoma line.SNK6 cells were cultured with Radicicol (A) or 17-AAG (B) at concentrations of 3, 1, 0.3 or 0.1 µM and cell numbers were counted on days 0, 2 and 4. Data are shown as the means of three independent replicates.
Mentions: After confirming that HSP90 inhibitors repress LMP1 expression in EBV-positive lymphoma cells, we then examined whether the inhibitors might actually suppress cancerous growth. We first tested at the cell culture level (Fig. 3). Three or 1 µM of Radicicol (Fig. 3A) or 17-AAG (Fig. 3B) could fully block proliferation of SNK6 cells depending on the concentration. Partial but appreciable inhibition was also exhibited at lower concentrations.

Bottom Line: We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells.Tumor formation in immuno-defficient NOD/Shi-scid/IL-2Rγ() (NOG) mice was also retarded.These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.

View Article: PubMed Central - PubMed

Affiliation: Division of Virology, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.

ABSTRACT
Epstein-Barr virus (EBV) LMP1 is a major oncoprotein expressed in latent infection. It functions as a TNFR family member and constitutively activates cellular signals, such as NFκB, MAPK, JAK/STAT and AKT. We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells. Tumor formation in immuno-defficient NOD/Shi-scid/IL-2Rγ() (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.

Show MeSH
Related in: MedlinePlus