Toggle Main Menu Toggle Search

Open Access padlockePrints

Apoptosis and tumor remission in liver tumor xenografts by 4-phenylbutyrate

Lookup NU author(s): Dr Frida Ponthan

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

4-phenylbutyrate (triButyrate trade mark, PB) a derivative of the short-chain fatty acid, butyrate, possesses anti-tumor activity in vitro in different tumor cell lines. Unlike most cytostatic compounds, PB possesses low toxicity. In order to evaluate possible clinical use of PB in cancer therapy, hepatocarcinoma (Hep3B) and hepatoblastoma (HepT1) cell lines, as well as xenografts derived from those in nude rats, were treated with PB in different dose (1-100 mM) and time regimens. Treatment with 10 mM of PB for 24 h (or 5 mM for 48 h) was shown to significantly inhibit Hep3B cell growth in vitro. The HepT1 cell line was more sensitive to PB treatment: already 1 mM of PB for 24 h significantly inhibited the growth of the cells. PB also resulted in regression of xenografts derived from these cell lines in vivo, when administrated by mini-pump with an intratumor catheter, yielding 20 micro mol of PB per cm3 of tumor volume per day. TUNEL assay and caspase-3 activity measurements suggested apoptosis to be the cell death mechanism in both cell lines and xenografts. Increased histones H3 and H4 acetylation was shown in both cells and xenografts, and the inhibition of histone deacetylase is proposed as the main trigger for the anti-tumor action of PB. Concomitant induction of p21Waf1/Cip1 expression was detected by RNase protection assay and Western blotting. Reduction in expression of alpha-fetoprotein was found both in Hep3B cells and xenografts, suggesting also a differentiation effect by PB.


Publication metadata

Author(s): Svechnikova I, Gray SG, Kundrotiene J, Ponthan FM, Kogner P, Ekström TJ

Publication type: Article

Publication status: Published

Journal: International Journal of Oncology

Year: 2003

Volume: 22

Issue: 3

Pages: 579-588

ISSN (print): 1019-6439

ISSN (electronic): 1791-2423

PubMed id: 12579311

Notes: Comparative Study Journal Article Research Support, Non-U.S. Gov't Greece


Share