Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice.
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.
Giermasz
Adam
A
Department of Immunology, Centre for Biostructure Research, The Medical University of Warsaw, Poland.
Makowski
Marcin
M
Kozłowska
Ewa
E
Nowis
Dominika
D
Maj
Małgorzata
M
Jalili
Ahmad
A
Feleszko
Wojciech
W
Wójcik
Cezary
C
Dabrowska
Anna
A
Jakóbisiak
Marek
M
Gołab
Jakub
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D005562:Formazans; D008148:Lovastatin / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013778:Tetrazolium Salts; D014280:Triglycerides / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D005562:Formazans; D013778:Tetrazolium Salts; D014280:Triglycerides; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C079782:MTT formazan; D008148:Lovastatin; C005830:tributyrin