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

20 Citations (Scopus)

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

Fingerprint

Lewis Lung Carcinoma
Lovastatin
Butyrates
Apoptosis
Cyclins
Butyric Acid
Prodrugs
Therapeutics
Hypercholesterolemia
Pharmaceutical Preparations
Antineoplastic Agents
Neoplasms
Cell Cycle
Theoretical Models
Growth
In Vitro Techniques

Keywords

  • Butyrate
  • Cancer
  • Lovastatin
  • Synergism
  • Tributyrin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice. / Giermasz, Adam; Makowski, Marcin; Kozłowska, Ewa; Nowis, Dominika; Maj, Małgorzata; Jalili, Ahmad; Feleszko, Wojciech; Wójcik, Cezary; Da̧rowska, Anna; Jakóbisiak, Marek; Goła̧b, Jakub.

In: International Journal of Cancer, Vol. 97, No. 6, 20.02.2002, p. 746-750.

Research output: Contribution to journalArticle

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, vol. 97, no. 6, pp. 746-750. https://doi.org/10.1002/ijc.10119
Giermasz, Adam ; Makowski, Marcin ; Kozłowska, Ewa ; Nowis, Dominika ; Maj, Małgorzata ; Jalili, Ahmad ; Feleszko, Wojciech ; Wójcik, Cezary ; Da̧rowska, Anna ; Jakóbisiak, Marek ; Goła̧b, Jakub. / Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice. In: International Journal of Cancer. 2002 ; Vol. 97, No. 6. pp. 746-750.
@article{36c32509b63c455c88e38d6cbd1de382,
title = "Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice",
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.",
keywords = "Butyrate, Cancer, Lovastatin, Synergism, Tributyrin",
author = "Adam Giermasz and Marcin Makowski and Ewa Kozłowska and Dominika Nowis and Małgorzata Maj and Ahmad Jalili and Wojciech Feleszko and Cezary W{\'o}jcik and Anna Da̧rowska and Marek Jak{\'o}bisiak and Jakub Goła̧b",
year = "2002",
month = "2",
day = "20",
doi = "10.1002/ijc.10119",
language = "English (US)",
volume = "97",
pages = "746--750",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice

AU - Giermasz, Adam

AU - Makowski, Marcin

AU - Kozłowska, Ewa

AU - Nowis, Dominika

AU - Maj, Małgorzata

AU - Jalili, Ahmad

AU - Feleszko, Wojciech

AU - Wójcik, Cezary

AU - Da̧rowska, Anna

AU - Jakóbisiak, Marek

AU - Goła̧b, Jakub

PY - 2002/2/20

Y1 - 2002/2/20

N2 - 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.

AB - 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.

KW - Butyrate

KW - Cancer

KW - Lovastatin

KW - Synergism

KW - Tributyrin

UR - http://www.scopus.com/inward/record.url?scp=0037138434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037138434&partnerID=8YFLogxK

U2 - 10.1002/ijc.10119

DO - 10.1002/ijc.10119

M3 - Article

C2 - 11857349

AN - SCOPUS:0037138434

VL - 97

SP - 746

EP - 750

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 6

ER -