Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice

Wojciech Feleszko, Izabela Młynarczuk, Ewa Z. Bałkowiec-Iskra, Anna Czajka, Tomasz Świtaj, Tomasz Stokłosa, Adam Giermasz, Marek Jakóbisiak

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Lovastatin, a drug commonly used in the clinic to treat hypercholesterolemia, has previously been reported to exert antitumor effects in rodent tumor models and to strengthen the antitumor effects of immune response modifiers (tumor necrosis factor α and IFN-γ) or chemotherapeutic drugs (cisplatin). In the present report, we show in three murine tumor cell lines (Colon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) that lovastatin can also effectively potentiate the cytostatic/cytotoxic activity of doxorubicin. In three tumor models (CoIon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) in vivo, we have demonstrated significantly increased sensitivity to the combined treatment with both lovastatin (15 mg/kg for 10 days) and doxorubicin (3 x 2.5 mg/kg; cumulative dose, 7.5 mg/kg) as compared with either agent acting alone. Lovastatin treatment also resulted in a significant reduction of troponin T release by cardiomyocytes in doxorubicin- treated mice. This observation is particularly interesting because lovastatin is known to reduce doxorubicin-induced cardiac injury.

Original languageEnglish (US)
Pages (from-to)2044-2052
Number of pages9
JournalClinical Cancer Research
Volume6
Issue number5
StatePublished - May 2000
Externally publishedYes

Fingerprint

Lovastatin
Doxorubicin
Lewis Lung Carcinoma
NIH 3T3 Cells
Neoplasms
Sarcoma
Troponin T
Cytostatic Agents
Hypercholesterolemia
Tumor Cell Line
Cardiac Myocytes
Pharmaceutical Preparations
Cisplatin
Rodentia
Colon
Tumor Necrosis Factor-alpha
Cardiotoxicity
Wounds and Injuries

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Feleszko, W., Młynarczuk, I., Bałkowiec-Iskra, E. Z., Czajka, A., Świtaj, T., Stokłosa, T., ... Jakóbisiak, M. (2000). Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice. Clinical Cancer Research, 6(5), 2044-2052.

Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice. / Feleszko, Wojciech; Młynarczuk, Izabela; Bałkowiec-Iskra, Ewa Z.; Czajka, Anna; Świtaj, Tomasz; Stokłosa, Tomasz; Giermasz, Adam; Jakóbisiak, Marek.

In: Clinical Cancer Research, Vol. 6, No. 5, 05.2000, p. 2044-2052.

Research output: Contribution to journalArticle

Feleszko, W, Młynarczuk, I, Bałkowiec-Iskra, EZ, Czajka, A, Świtaj, T, Stokłosa, T, Giermasz, A & Jakóbisiak, M 2000, 'Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice', Clinical Cancer Research, vol. 6, no. 5, pp. 2044-2052.
Feleszko W, Młynarczuk I, Bałkowiec-Iskra EZ, Czajka A, Świtaj T, Stokłosa T et al. Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice. Clinical Cancer Research. 2000 May;6(5):2044-2052.
Feleszko, Wojciech ; Młynarczuk, Izabela ; Bałkowiec-Iskra, Ewa Z. ; Czajka, Anna ; Świtaj, Tomasz ; Stokłosa, Tomasz ; Giermasz, Adam ; Jakóbisiak, Marek. / Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 5. pp. 2044-2052.
@article{ea12004388324cdbbdbe337bb5be6039,
title = "Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice",
abstract = "Lovastatin, a drug commonly used in the clinic to treat hypercholesterolemia, has previously been reported to exert antitumor effects in rodent tumor models and to strengthen the antitumor effects of immune response modifiers (tumor necrosis factor α and IFN-γ) or chemotherapeutic drugs (cisplatin). In the present report, we show in three murine tumor cell lines (Colon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) that lovastatin can also effectively potentiate the cytostatic/cytotoxic activity of doxorubicin. In three tumor models (CoIon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) in vivo, we have demonstrated significantly increased sensitivity to the combined treatment with both lovastatin (15 mg/kg for 10 days) and doxorubicin (3 x 2.5 mg/kg; cumulative dose, 7.5 mg/kg) as compared with either agent acting alone. Lovastatin treatment also resulted in a significant reduction of troponin T release by cardiomyocytes in doxorubicin- treated mice. This observation is particularly interesting because lovastatin is known to reduce doxorubicin-induced cardiac injury.",
author = "Wojciech Feleszko and Izabela Młynarczuk and Bałkowiec-Iskra, {Ewa Z.} and Anna Czajka and Tomasz Świtaj and Tomasz Stokłosa and Adam Giermasz and Marek Jak{\'o}bisiak",
year = "2000",
month = "5",
language = "English (US)",
volume = "6",
pages = "2044--2052",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice

AU - Feleszko, Wojciech

AU - Młynarczuk, Izabela

AU - Bałkowiec-Iskra, Ewa Z.

AU - Czajka, Anna

AU - Świtaj, Tomasz

AU - Stokłosa, Tomasz

AU - Giermasz, Adam

AU - Jakóbisiak, Marek

PY - 2000/5

Y1 - 2000/5

N2 - Lovastatin, a drug commonly used in the clinic to treat hypercholesterolemia, has previously been reported to exert antitumor effects in rodent tumor models and to strengthen the antitumor effects of immune response modifiers (tumor necrosis factor α and IFN-γ) or chemotherapeutic drugs (cisplatin). In the present report, we show in three murine tumor cell lines (Colon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) that lovastatin can also effectively potentiate the cytostatic/cytotoxic activity of doxorubicin. In three tumor models (CoIon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) in vivo, we have demonstrated significantly increased sensitivity to the combined treatment with both lovastatin (15 mg/kg for 10 days) and doxorubicin (3 x 2.5 mg/kg; cumulative dose, 7.5 mg/kg) as compared with either agent acting alone. Lovastatin treatment also resulted in a significant reduction of troponin T release by cardiomyocytes in doxorubicin- treated mice. This observation is particularly interesting because lovastatin is known to reduce doxorubicin-induced cardiac injury.

AB - Lovastatin, a drug commonly used in the clinic to treat hypercholesterolemia, has previously been reported to exert antitumor effects in rodent tumor models and to strengthen the antitumor effects of immune response modifiers (tumor necrosis factor α and IFN-γ) or chemotherapeutic drugs (cisplatin). In the present report, we show in three murine tumor cell lines (Colon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) that lovastatin can also effectively potentiate the cytostatic/cytotoxic activity of doxorubicin. In three tumor models (CoIon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) in vivo, we have demonstrated significantly increased sensitivity to the combined treatment with both lovastatin (15 mg/kg for 10 days) and doxorubicin (3 x 2.5 mg/kg; cumulative dose, 7.5 mg/kg) as compared with either agent acting alone. Lovastatin treatment also resulted in a significant reduction of troponin T release by cardiomyocytes in doxorubicin- treated mice. This observation is particularly interesting because lovastatin is known to reduce doxorubicin-induced cardiac injury.

UR - http://www.scopus.com/inward/record.url?scp=0034124301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034124301&partnerID=8YFLogxK

M3 - Article

C2 - 10815931

AN - SCOPUS:0034124301

VL - 6

SP - 2044

EP - 2052

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 5

ER -