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

114 Scopus citations

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

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice'. Together they form a unique fingerprint.

  • Cite this

    Feleszko, W., Młynarczuk, I., Bałkowiec-Iskra, E. Z., 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, 6(5), 2044-2052.