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

  • Authors:
    • Irina Svechnikova
    • Steven G. Gray
    • Jurgita Kundrotiene
    • Frida Ponthan
    • Per Kogner
    • Tomas J. Ekström
  • View Affiliations

  • Published online on: March 1, 2003     https://doi.org/10.3892/ijo.22.3.579
  • Pages: 579-588
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Abstract

4-Phenylbutyrate (triButyrate™, 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 µmol 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 α-fetoprotein was found both in Hep3B cells and xenografts, suggesting also a differentiation effect by PB.

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March 2003
Volume 22 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Svechnikova I, Gray SG, Kundrotiene J, Ponthan F, Kogner P and Ekström TJ: Apoptosis and tumor remission in liver tumor xenografts by 4-phenylbutyrate. Int J Oncol 22: 579-588, 2003
APA
Svechnikova, I., Gray, S.G., Kundrotiene, J., Ponthan, F., Kogner, P., & Ekström, T.J. (2003). Apoptosis and tumor remission in liver tumor xenografts by 4-phenylbutyrate. International Journal of Oncology, 22, 579-588. https://doi.org/10.3892/ijo.22.3.579
MLA
Svechnikova, I., Gray, S. G., Kundrotiene, J., Ponthan, F., Kogner, P., Ekström, T. J."Apoptosis and tumor remission in liver tumor xenografts by 4-phenylbutyrate". International Journal of Oncology 22.3 (2003): 579-588.
Chicago
Svechnikova, I., Gray, S. G., Kundrotiene, J., Ponthan, F., Kogner, P., Ekström, T. J."Apoptosis and tumor remission in liver tumor xenografts by 4-phenylbutyrate". International Journal of Oncology 22, no. 3 (2003): 579-588. https://doi.org/10.3892/ijo.22.3.579