Lovastatin enhances the antitumoral and apoptotic activity of doxorubicin in murine tumor models

Abstract

Abstract. Despite its effectiveness as an antineoplastic drug, doxorubicin (DOX) is usually associated with cardiotoxicity. Lovastatin (LOV), a hypolipidemic agent used in the clinic, has been demonstrated to have antitumoral and antimetastatic effects in murine models. Since the two agents arrest tumor cells in different phases of the cell cycle and induce apoptosis, the goal of this study was to examine the efficacy of a combination therapy with LOV and low doses of DOX, in an attempt to obtain an improved antitumoral effect devoid of toxicity, by using a rat B-cell lymphoma and a mouse mammary tumor. In the two models, the combined treatment showed a synergistic antitumoral effect, which is mainly ascribed to an increased apoptotic response elicited by a LOV/DOX combination than either agent alone. The therapeutic benefit demonstrated by the combination treatment is further emphasized by the lack of toxicity.

Differential interactions between statins and P‐glycoprotein: Implications for exploiting statins as anticancer agents

“…If lovastatin is coadministered with P‐gp substrates, there exists the possibility that inhibiting the physiological function of P‐gp may result in decreased elimination of the substrate, requiring dose reduction. However, lovastatin and doxorubicin have been coadministered in mice with no noted adverse toxicity 57, 58. Further evaluation of lovastatin in combination with chemotherapeutic agents that are P‐gp substrates for the treatment of MDR tumors is therefore warranted to examine whether the therapeutic potentiation observed in cell culture models is replicated in vivo .…”

HMG-CoA reductase inhibitors as adjuvant treatment for hematologic malignancies: what is the current evidence?

“…In a study using rat B-cell lymphoma cells, Rozados et al demonstrated that low doses of lovastatin as a single agent decreased tumor cell viability in vitro. Notably, use of lovastatin in combination with doxorubicin induced a significant increase in cytotoxicity when compared to the effect of each agent given alone [90].…”

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

“…Statins were able to potentiate the antitumor effects of anthracyclines in both cellular and animal models. In mice, lovastatin synergistically potentiated doxorubicin-induced cytotoxicity in colon and breast carcinoma (Feleszko et al, 2000;Rozados et al, 2008) and showed an additive effect in lung cancer cell lines (Feleszko et al, 2000). Similar synergistic effects with different anthracyclines were also found for simvastatin and fluvastatin in human rhabdomyosarcoma cells (Werner et al, 2004) and breast cancer cell lines (Budman et al, 2007), respectively.…”