Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice

Adam Giermasz, Marcin Makowski, Ewa Kozłowska, Dominika Nowis, Małgorzata Maj, Ahmad Jalili, Wojciech Feleszko, Cezary Wójcik, Anna Da̧rowska, Marek Jakóbisiak, Jakub Goła̧b

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Lovastatin, the drug used for the treatment of hypercholesterolemia, has previously been reported to exert antitumor activity in experimental murine models. Butyrate and butyric acid derivatives are well known to induce differentiation and apoptosis of tumour cells and also have recently gained acceptance as potential anticancer agents. In this study, we examined the antitumor effects of the combination of lovastatin and butyrate or its prodrug tributyrin in vitro and in vivo against a murine Lewis lung carcinoma (3LL). This combination therapy showed synergistic antitumor activity against 3LL cells in vitro. These effects were at least in part due to apoptosis induction that occurred after 12 hr of incubation with lovastatin and butyrate and was preceded by changes in cell cycle distribution of treated cells and expression of p21, p53 and cyclin DI. Remarkably, a systemic treatment of syngeneic mice inoculated with 3LL cells with both drugs resulted in significant tumour growth retardation.

Original languageEnglish (US)
Pages (from-to)746-750
Number of pages5
JournalInternational Journal of Cancer
Volume97
Issue number6
DOIs
StatePublished - Feb 20 2002
Externally publishedYes

Keywords

  • Butyrate
  • Cancer
  • Lovastatin
  • Synergism
  • Tributyrin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Giermasz, A., Makowski, M., Kozłowska, E., Nowis, D., Maj, M., Jalili, A., Feleszko, W., Wójcik, C., Da̧rowska, A., Jakóbisiak, M., & Goła̧b, J. (2002). Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice. International Journal of Cancer, 97(6), 746-750. https://doi.org/10.1002/ijc.10119