Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells

Ishida, Koichi; Yamazaki, Tomohiro; Motohashi, Kazuki; Kobayashi, Miho; Matsuo, Junji; Osaki, Takako; Hanawa, Tomoko; Kamiya, Shigeru; Yamamoto, Yoshimasa; Yamaguchi, Hiroyuki

doi:10.1007/s10156-011-0274-6

Cited by 3 publications

(2 citation statements)

References 28 publications

(37 reference statements)

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“…Mifepristone inhibited the RNA expression level of HSP60 in HEp-2 cells [4]. Additionally, HSP60 silencing decreased survivin expression in HCC cells [2].…”

Section: Mifepristone Promotes the Release Of Hsp60 From Mitochondria...mentioning

confidence: 96%

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Mifepristone inhibits hepatoma growth by enhancing the GR-HSP60-survivin interaction to facilitate survivin degradation

Huang,

Lin,

Lai

et al. 2023

J. Cancer

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Silencing of heat shock protein 60 (HSP60) suppresses the growth of hepatocellular carcinoma (HCC). Mifepristone inhibits HSP60 mRNA expression in Chlamydophila -infected epithelial cells. The aim of this study was to determine whether mifepristone could inhibit the growth of HCC cells by affecting the functions of HSP60. The effect of mifepristone on cell viability was examined by flow cytometry and a cell proliferation assay. Protein-protein interactions were examined using the immunoprecipitation assay. The anti-tumor effect of mifepristone was evaluated using a xenograft model. Our results indicated that mifepristone induces cell cycle arrest at the G1 phase and early-stage apoptosis in HCC cells. Instead of reducing the total amount of HSP60, mifepristone induced the release of mitochondrial HSP60 into the cytosol by causing a loss of ΔΨm, thereby enhancing glucocorticoid receptor (GR)-HSP60-survivin complex formation as well as survivin degradation. Animal models have confirmed the growth inhibitory effects of mifepristone on HCC, including changes in the abundance of HSP60 in mitochondria and cytosol, decreased survivin and Ki-67-positive cells, as well as increased cell apoptosis. In conclusion, the inhibition of HCC growth by mifepristone may be achieved by altering the subcellular distribution of HSP60 to enhance the formation of cytosolic GR-HSP60-survivin complexes in the cells, leading to the degradation of survivin.

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“…Mifepristone inhibited the RNA expression level of HSP60 in HEp-2 cells [4]. Additionally, HSP60 silencing decreased survivin expression in HCC cells [2].…”

Section: Mifepristone Promotes the Release Of Hsp60 From Mitochondria...mentioning

confidence: 96%

“…These findings suggest that HSP60 may represent a potential therapeutic target for HCC. Additionally, in 2012, a study reported that mifepristone decreased HSP60 mRNA expression in HEp-2 cells infected with Chlamydophila and treated with IFNγ 4 , suggesting that mifepristone might act as an inhibitor of HSP60.…”

Section: Introductionmentioning

confidence: 99%