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 language | English (US) |
|---|---|
| Pages (from-to) | 2044-2052 |
| Number of pages | 9 |
| Journal | Clinical Cancer Research |
| Volume | 6 |
| Issue number | 5 |
| State | Published - May 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Medicine(all)
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
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.
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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 -