Phenylbutyrate inhibits growth of cervical carcinoma cells independent of HPV type and copy number

Inhibitors of histone deacetylase, such as sodium butyrate, block proliferation of cervical carcinoma cells by inhibiting the G1 to S transition of the cell cycle. The derivative phenylbutyrate (PB), characterized by its higher pharmacological half-life, and its metabolite phenylacetate (PA) were te...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2003-02, Vol.129 (2), p.107-113
Main Authors: FINZER, P, STÖHR, M, SEIBERT, N, RÖSL, F
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biological and medical sciences
Blotting, Western
Carcinoma - drug therapy
Carcinoma - virology
Cells
Cervical cancer
Chemotherapy
Female
Flow Cytometry
Humans
Medical sciences
Papillomaviridae - classification
Papillomavirus Infections - complications
Pharmacology. Drug treatments
Phenylbutyrates - pharmacology
Precancerous Conditions - drug therapy
Precancerous Conditions - virology
Protease inhibitors
Tumor Virus Infections - complications
Uterine Cervical Neoplasms - drug therapy
Uterine Cervical Neoplasms - virology
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Summary:Inhibitors of histone deacetylase, such as sodium butyrate, block proliferation of cervical carcinoma cells by inhibiting the G1 to S transition of the cell cycle. The derivative phenylbutyrate (PB), characterized by its higher pharmacological half-life, and its metabolite phenylacetate (PA) were tested for their growth-inhibitory function on cervical cancer cells differing in their HPV type, copy number, and integration sites. Using flow cytometric and Western blot analyses, we show that a 24-h incubation period with PB, but not with PA, was already sufficient to cause a dose-dependent growth arrest by increasing the G1 fraction with a concomitant drop in the S-phase. Consistent with the cell cycle block, only PB, but not PA, induced the cyclin-dependent kinase inhibitors p21(CIP1) and p27(KIP1). The inhibitory effect was not the result of a non-specific cytotoxic effect of PB, since cessation of cellular growth was already completely reversible 5 h after drug removal. Due to its broad growth inhibitory properties on different cervical carcinoma cells in vitro, and its low toxic profile demonstrated in preceding clinical studies, PB may serve as an effective drug in handling pre-cancerous lesions and cervical cancer in patients.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-003-0416-z