Cerivastatin demonstrates enhanced antitumor activity against human breast cancer cell lines when used in combination with doxorubicin or cisplatin

  • Authors:
    • Katarzyna Kozar
    • Rafal Kaminski
    • Magdalena Legat
    • Maciej Kopec
    • Dominika Nowis
    • Janusz S. Skierski
    • Miroslawa Koronkiewicz
    • Marek Jakóbisiak
    • Jakub Golab
  • View Affiliations

  • Published online on: May 1, 2004     https://doi.org/10.3892/ijo.24.5.1149
  • Pages: 1149-1157
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase are commonly used in the clinic to treat hypercholesterolemia and have been reported to exert antitumor effects. Cerivastatin is a novel, synthetic and the most pharmacologically potent inhibitor of HMG-CoA reductase. We decided to examine the cytostatic/cytotoxic activity of cerivastatin against human breast cancer cell lines and to test whether the effects of cerivastatin could be potentiated by doxorubicin and cisplatin. Cytostatic/cytotoxic effects of cerivastatin used alone or in the combination with chemotherapeutics were measured with MTT assay. The cell cycle distribution and apoptosis induction were evaluated with flow cytometer. The expression of p21 and p27 cyclin-dependent kinase inhibitors was measured with Western blotting. Isobologram analysis was performed to study the drug interactions. We observed that cerivastatin exerts cytostatic/cytotoxic effects against four human tumor cell lines (T-47D, T4-2, MDA-MB-231, MCF-7). We also demonstrated that cerivastatin exerts growth inhibitory effect through induction of p21 cyclin-dependent kinase inhibitor and inhibition of cell cycle progression. In the two tumor cell lines studied, one sensitive (MDA-MB-231) and one moderately resistant (T4-2) to the cytostatic/cytotoxic effects of cerivastatin we examined the effects of combined treatment with cerivastatin and either doxorubicin or cisplatin. Cerivastatin potentiated cytostatic/cytotoxic effects of cisplatin against T4-2 cells and those of doxorubicin against both cell lines. In T4-2 cells the interaction between doxorubicin and cerivastatin and between cisplatin and cerivastatin was found to be synergistic. Altogether, these studies indicate that cerivastatin is another HMG-CoA reductase inhibitor with potent antitumor effects.

Related Articles

Journal Cover

May 2004
Volume 24 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Kozar, K., Kaminski, R., Legat, M., Kopec, M., Nowis, D., Skierski, J.S. ... Golab, J. (2004). Cerivastatin demonstrates enhanced antitumor activity against human breast cancer cell lines when used in combination with doxorubicin or cisplatin. International Journal of Oncology, 24, 1149-1157. https://doi.org/10.3892/ijo.24.5.1149
MLA
Kozar, K., Kaminski, R., Legat, M., Kopec, M., Nowis, D., Skierski, J. S., Koronkiewicz, M., Jakóbisiak, M., Golab, J."Cerivastatin demonstrates enhanced antitumor activity against human breast cancer cell lines when used in combination with doxorubicin or cisplatin". International Journal of Oncology 24.5 (2004): 1149-1157.
Chicago
Kozar, K., Kaminski, R., Legat, M., Kopec, M., Nowis, D., Skierski, J. S., Koronkiewicz, M., Jakóbisiak, M., Golab, J."Cerivastatin demonstrates enhanced antitumor activity against human breast cancer cell lines when used in combination with doxorubicin or cisplatin". International Journal of Oncology 24, no. 5 (2004): 1149-1157. https://doi.org/10.3892/ijo.24.5.1149