Lovastatin enhances the antitumoral and apoptotic activity of doxorubicin in murine tumor models.
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.
Rozados
Viviana R
VR
Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, (2000) Rosario, Argentina.
Hinrichsen
Lucila I
LI
Binda
M Mercedes
MM
Gervasoni
Silvia I
SI
Matar
Pablo
P
Bonfil
R Daniel
RD
Scharovsky
O Graciela
OG
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D004357:Drug Synergism; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000008:administration & dosage*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004317:Doxorubicin; D008148:Lovastatin