Cited by 10Histone Deacetylase Inhibitors ResearchHeat shock proteins researchAdvanced Proteomics Techniques and Applications

Proteomic study identified HSP 70kDa protein 1A as a possible therapeutic target, in combination with histone deacetylase inhibitors, for lymphoid neoplasms

Fujii, Kazuyasu, Suzuki, Norihiro, Ikeda, Kazuko, Hamada, Toshihisa, Yamamoto, Takenobu, Kondo, Tadashi, Iwatsuki, Keiji·2012·Journal of Proteomics

Abstract

Histone deacetylase inhibitors (HDACi) demonstrate possible anticancer activities in various malignancies including lymphoid neoplasms. However, the anticancer effects of HDACi are often limited, and combination therapy with other drugs has been undertaken to improve the outcome of patients. Here we conducted proteomic investigation of 33 lymphoid cell lines to identify novel therapeutic targets for enhancing the effects of HDACi. Using the proteomic data in our published 2D-DIGE database, we examined the proteins associated with resistance to valproic acid (VPA). The lymphoid neoplasm cell lines in the database were grouped according to their sensitivity to VPA treatment. A comparative proteomic study of the cell line groups resulted in the identification of 10 protein spots, whose intensity was associated with chemosensitivity. Among the identified proteins, HSPA1A showed higher expression in cell lines with resistance to VPA, and the results were validated by Western blotting. In vitro experiments demonstrated that treatment with KNK-437, an inhibitor of HSPA1A, enhanced the cytotoxic effects of VPA, as well as vorinostat, in the lymphoid neoplasm cell line. Treatment with KNK-437 facilitated the apoptotic effects of VPA. In conclusion, we identified HSPA1A as a possible therapeutic target, in combination with HDACi, for lymphoid neoplasms.

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Crossref · 10.1016/j.jprot.2011.11.010

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Authors
Fujii, K., Suzuki, N., Ikeda, K., Hamada, T., Yamamoto, T., Kondo, T., & Iwatsuki, K.
Affiliations
  • Okayama University (JP)
  • National Cancer Center Research Institute (JP)
Corresponding author
Fujii, Kazuyasu
Venue
Journal of Proteomics
Publisher
Elsevier BV
Published
2012-02
Volume
75
Issue
4
Pages
1401-1410
ISSN
1874-3919 (ISSN-L)
OpenAlex
W2058844949
Cited by
10
References
40
Citations by year
2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2015: 1 · 2013: 1
FWCI
0.13
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Proteomics (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (24591626)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
HSPA1A, HSP70, histone deacetylase inhibitors, valproic acid, vorinostat, lymphoid malignancies, drug resistance, combination therapy, therapeutic target, apoptosis, lymphoid cell lines, proteomic profiling
MeSH terms
Antineoplastic Agents, Drug Screening Assays, Antitumor, Humans, Lymphoma, Valproic Acid, Blotting, Western, Apoptosis, HSP70 Heat-Shock Proteins, Inhibitory Concentration 50, Proteomics, Cell Line, Tumor, Histone Deacetylase Inhibitors

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