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Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5-fluorouracil in colorectal cancer cells.

Matsunaga A, Ishii Y, Tsuruta M, Okabayashi K, Hasegawa H, Kitagawa Y - Oncol Lett (2014)

Bottom Line: By contrast, exposure to 5-FU in HT29 cells expressing a low level of HSP27 with a high 5-FU sensitivity marginally increased HSP27 expression, with minimal phosphorylation.Treatment with a selective inhibitor, p38 mitogen-activated protein kinase (MAPK; SB203580), caused the dose-dependent suppression of HSP27 phosphorylation, which was upregulated by 5-FU, reducing the half maximal inhibitory concentration values of 5-FU in the HCT116 and HCT15 cells.However, treatment with SB203580 exhibited no significant effect on cell growth or survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.

ABSTRACT
The aim of the present study was to investigate whether the inhibition of HSP27 phosphorylation, which affects certain cellular functions, modulates sensitivity to 5-fluorouracil (5-FU) in colorectal cancer cells. Exposure to 5-FU in HCT116 and HCT15 cells expressing high levels of HSP27 with a low 5-FU sensitivity caused a minimal change in HSP27 expression, but induced the upregulation of HSP27 phosphorylation, particularly at Ser78. By contrast, exposure to 5-FU in HT29 cells expressing a low level of HSP27 with a high 5-FU sensitivity marginally increased HSP27 expression, with minimal phosphorylation. Treatment with a selective inhibitor, p38 mitogen-activated protein kinase (MAPK; SB203580), caused the dose-dependent suppression of HSP27 phosphorylation, which was upregulated by 5-FU, reducing the half maximal inhibitory concentration values of 5-FU in the HCT116 and HCT15 cells. However, treatment with SB203580 exhibited no significant effect on cell growth or survival. In conclusion, this study indicated that the inhibition of HSP27 phosphorylation by a selective inhibitor of p38 MAPK promotes 5-FU sensitivity without causing cytotoxicity in colorectal cancer cells.

No MeSH data available.


Related in: MedlinePlus

Cell growth assay following SB203580 treatment. The cells were treated with various concentrations of SB203580 (0, 1, 10 and 50 μM), and viable cells were counted for four days. No significant differences in the cell growth of the three cell lines was identified among the various SB203580 concentrations used. (A) HCT116; (B) HCT15; and (C) HT29. HSP, heat shock protein; 5-FU, 5-fluorouracil; SB, SB203580; DMSO, dimethyl sulfoxide.
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f3-ol-08-06-2496: Cell growth assay following SB203580 treatment. The cells were treated with various concentrations of SB203580 (0, 1, 10 and 50 μM), and viable cells were counted for four days. No significant differences in the cell growth of the three cell lines was identified among the various SB203580 concentrations used. (A) HCT116; (B) HCT15; and (C) HT29. HSP, heat shock protein; 5-FU, 5-fluorouracil; SB, SB203580; DMSO, dimethyl sulfoxide.

Mentions: To investigate the effect of SB203580 on cell growth or survival, a cell growth assay was performed using a count of viable cells. Three colorectal cancer cell lines were examined following treatment with various concentrations of SB203580 (0, 1, 10 or 50 μM) in RPMI-1640 containing 5% FBS (Fig. 3). As a result, SB203580 treatment exhibited no significant effect on cell growth or survival in the cell lines.


Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5-fluorouracil in colorectal cancer cells.

Matsunaga A, Ishii Y, Tsuruta M, Okabayashi K, Hasegawa H, Kitagawa Y - Oncol Lett (2014)

Cell growth assay following SB203580 treatment. The cells were treated with various concentrations of SB203580 (0, 1, 10 and 50 μM), and viable cells were counted for four days. No significant differences in the cell growth of the three cell lines was identified among the various SB203580 concentrations used. (A) HCT116; (B) HCT15; and (C) HT29. HSP, heat shock protein; 5-FU, 5-fluorouracil; SB, SB203580; DMSO, dimethyl sulfoxide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214436&req=5

f3-ol-08-06-2496: Cell growth assay following SB203580 treatment. The cells were treated with various concentrations of SB203580 (0, 1, 10 and 50 μM), and viable cells were counted for four days. No significant differences in the cell growth of the three cell lines was identified among the various SB203580 concentrations used. (A) HCT116; (B) HCT15; and (C) HT29. HSP, heat shock protein; 5-FU, 5-fluorouracil; SB, SB203580; DMSO, dimethyl sulfoxide.
Mentions: To investigate the effect of SB203580 on cell growth or survival, a cell growth assay was performed using a count of viable cells. Three colorectal cancer cell lines were examined following treatment with various concentrations of SB203580 (0, 1, 10 or 50 μM) in RPMI-1640 containing 5% FBS (Fig. 3). As a result, SB203580 treatment exhibited no significant effect on cell growth or survival in the cell lines.

Bottom Line: By contrast, exposure to 5-FU in HT29 cells expressing a low level of HSP27 with a high 5-FU sensitivity marginally increased HSP27 expression, with minimal phosphorylation.Treatment with a selective inhibitor, p38 mitogen-activated protein kinase (MAPK; SB203580), caused the dose-dependent suppression of HSP27 phosphorylation, which was upregulated by 5-FU, reducing the half maximal inhibitory concentration values of 5-FU in the HCT116 and HCT15 cells.However, treatment with SB203580 exhibited no significant effect on cell growth or survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.

ABSTRACT
The aim of the present study was to investigate whether the inhibition of HSP27 phosphorylation, which affects certain cellular functions, modulates sensitivity to 5-fluorouracil (5-FU) in colorectal cancer cells. Exposure to 5-FU in HCT116 and HCT15 cells expressing high levels of HSP27 with a low 5-FU sensitivity caused a minimal change in HSP27 expression, but induced the upregulation of HSP27 phosphorylation, particularly at Ser78. By contrast, exposure to 5-FU in HT29 cells expressing a low level of HSP27 with a high 5-FU sensitivity marginally increased HSP27 expression, with minimal phosphorylation. Treatment with a selective inhibitor, p38 mitogen-activated protein kinase (MAPK; SB203580), caused the dose-dependent suppression of HSP27 phosphorylation, which was upregulated by 5-FU, reducing the half maximal inhibitory concentration values of 5-FU in the HCT116 and HCT15 cells. However, treatment with SB203580 exhibited no significant effect on cell growth or survival. In conclusion, this study indicated that the inhibition of HSP27 phosphorylation by a selective inhibitor of p38 MAPK promotes 5-FU sensitivity without causing cytotoxicity in colorectal cancer cells.

No MeSH data available.


Related in: MedlinePlus