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A Comparative study of two histone deacetylase inhibitors, CG‐1521 and SAHA, on LNCaP and MCF‐7 cells
Author(s) -
Taylor Travis,
Knutson Andrew,
Welsh Jennifer,
Roy Somdutta,
Tenniswood Martin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a259-b
Subject(s) - lncap , cancer research , cell cycle , histone deacetylase , programmed cell death , cell growth , cyclin d1 , cell cycle checkpoint , prostate cancer , cyclin b1 , cancer cell , biology , apoptosis , chemistry , cancer , cyclin dependent kinase 1 , histone , gene , genetics , biochemistry
In addition to histones, HDAC inhibitors target the transcription factor p53 and its downstream targets. A number of hydroxamic acid derivatives, including SAHA and CG‐1521 are currently being developed as adjuvant treatments for a variety of cancers. The effects of SAHA and CG‐1521, on cell cycle, apoptosis and gene expression have been evaluated in two p53+/+ cell lines: LNCaP prostate cancer and MCF‐7 breast cancer cells. As characterized by flow cytometry, CG‐1521 induces G2/M arrest and cell death (as measured by apo‐BrdU incorporation), whereas SAHA induces G1/S arrest but not cell death. In LNCaP cells the CG‐1521 and SAHA differentially regulate genes involved in cell cycle and cell death. While both drugs upregulate p21 gene expression, several other cell cycle genes including Cyclin B1, Wee1, Cdc20, Plk1, Cyclin D1 and Cdc25a are modulated only by CG‐1521. CG‐1521 also modulates the expression of several cell death genes including Survivin, Gadd45a, Bnip3, Bnip3l, Pig3 and p21B in LNCaP cells, whereas SAHA has no effect on the expression of these genes. This study demonstrates that that prostate and breast cancer cells have very different cellular responses to the two HDAC inhibitors and they elicit very different responses at the transcriptional level of two HDAC inhibitors, demonstrating the potential of developing highly targeted adjuvant therapies for prostate and breast cancer. (Supported by the Coleman Foundation and Errant Gene Therapeutics)