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Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice
Author(s) -
Giermasz Adam,
Makowski Marcin,
Kozłowska Ewa,
Nowis Dominika,
Maj Małgorzata,
Jalili Ahmad,
Feleszko Wojciech,
Wójcik Cezary,
Dąbrowska Anna,
Jakóbisiak Marek,
Gołąb Jakub
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10119
Subject(s) - lovastatin , butyrate , lewis lung carcinoma , in vivo , apoptosis , pharmacology , cancer research , prodrug , in vitro , cell cycle , combination therapy , medicine , chemistry , biology , cancer , biochemistry , cholesterol , microbiology and biotechnology , fermentation , metastasis
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 D1. Remarkably, a systemic treatment of syngeneic mice inoculated with 3LL cells with both drugs resulted in significant tumour growth retardation. © 2001 Wiley‐Liss, Inc.