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


RESULTS
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.


CONCLUSIONS
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.
Finzer
P
P
Forschungsschwerpunkt Angewandte Tumorvirologie, Abteilung: Virale Transformationsmechanismen, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany. p.finzer@dkfz-heidelberg.de
Stöhr
M
M
Seibert
N
N
Rösl
F
F
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D027383:Papillomaviridae / Q000145:classification*; D030361:Papillomavirus Infections / Q000150:complications; D010654:Phenylbutyrates / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000821:virology; D014412:Tumor Virus Infections / Q000150:complications; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000821:virology
D000970:Antineoplastic Agents; D010654:Phenylbutyrates