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Blockade of GRP78 Translocation to the Cell Surface by HDAC6 Inhibition Suppresses Proliferation of Cholangiocarcinoma Cells.
- Source :
-
Anticancer research [Anticancer Res] 2022 Jan; Vol. 42 (1), pp. 471-482. - Publication Year :
- 2022
-
Abstract
- Background/aim: HDAC6, a cytoplasmic localized deacetylase, is a positive regulator of cancer progression via modification of various substrates. We evaluated how the interaction between HDAC6 and glucose regulatory protein 78 (GRP78) affects the growth of cholangiocarcinoma (CCA).<br />Materials and Methods: The anti-tumor effects of ACY-1215, an HDAC6 specific inhibitor, in CCA cell lines were analyzed by cell viability assay, western blotting, flow cytometry, co-immunoprecipitation, and biotinylation assays. In vivo effects of ACY-1215 were evaluated in a xenograft model using CCA cell line TFK-1.<br />Results: ACY-1215 increased the acetyl-form of GRP78 by approximately 50% compared to control, which impaired the translocation of GRP78 to the plasma membrane by 50% through alteration of cellular proliferative signaling via PI3K/AKT. Furthermore, ACY-1215 suppressed tumor growth by 50% compared to vehicle control in a CCA xenograft model.<br />Conclusion: Increase in GRP78 acetylation by HDAC6 inhibition suppressed GRP78 translocation to the cell surface, which inhibited proliferation and promoted apoptosis in CCA.<br /> (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Subjects :
- Animals
Cell Line, Tumor
Cell Membrane drug effects
Cell Membrane genetics
Cell Survival drug effects
Cholangiocarcinoma genetics
Cholangiocarcinoma pathology
Endoplasmic Reticulum Chaperone BiP antagonists & inhibitors
Flow Cytometry
Humans
Hydroxamic Acids pharmacology
Mice
Phosphatidylinositol 3-Kinases genetics
Protein Transport drug effects
Proto-Oncogene Proteins c-akt genetics
Pyrimidines pharmacology
Xenograft Model Antitumor Assays
Cell Proliferation drug effects
Cholangiocarcinoma drug therapy
Endoplasmic Reticulum Chaperone BiP genetics
Histone Deacetylase 6 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-7530
- Volume :
- 42
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 34969757
- Full Text :
- https://doi.org/10.21873/anticanres.15505