BACKGROUND: Cholesterol is essential for cell viability and growth. Interference with the cholesterol biosynthetic pathway with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (e.g., lovastatin) may preferentially slow malignant cell growth and offer a new approach to cancer chemotherapy. To test this hypothesis, we evaluated the effect of lovastatin alone, and as an adjuvant chemotherapeutic agent, on the growth and function of hepatoma tissue culture-4 (HTC-4) cells. METHODS: HTC-4 cells were treated with lovastatin at concentrations of 1, 3, 5, and 10 microM, with mitomycin-C at concentrations of 10, 25, 50, and 100 nM, or with combinations of the two drugs. Cell growth was evaluated by daily cell counts and substrate adhesion to fibronectin. RESULTS: Lovastatin alone slowed HTC-4 cell growth at concentrations as low as 1 microM (p < 0.01). Mitomycin-C alone slowed HTC-4 cell growth at concentrations of 25 nM and above (p < 0.01). Lovastatin added to mitomycin-C-treated cells resulted in a significant adjuvant effect, with cell growth slowed by an additional 20-30% by 1 microM lovastatin and by an additional 43-63% by 5 microM lovastatin, compared to mitomycin-C alone (p < 0.01). Lovastatin-treated cells also exhibited decreased adherence to substrate (p < 0.05). CONCLUSIONS: Lovastatin is effective alone and as an adjuvant to mitomycin-C in slowing the growth of HTC-4 cells. These in vitro results support further investigation of lovastatin as an adjuvant chemotherapeutic agent in animal models.
BACKGROUND:Cholesterol is essential for cell viability and growth. Interference with the cholesterol biosynthetic pathway with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (e.g., lovastatin) may preferentially slow malignant cell growth and offer a new approach to cancer chemotherapy. To test this hypothesis, we evaluated the effect of lovastatin alone, and as an adjuvant chemotherapeutic agent, on the growth and function of hepatoma tissue culture-4 (HTC-4) cells. METHODS: HTC-4 cells were treated with lovastatin at concentrations of 1, 3, 5, and 10 microM, with mitomycin-C at concentrations of 10, 25, 50, and 100 nM, or with combinations of the two drugs. Cell growth was evaluated by daily cell counts and substrate adhesion to fibronectin. RESULTS:Lovastatin alone slowed HTC-4 cell growth at concentrations as low as 1 microM (p < 0.01). Mitomycin-C alone slowed HTC-4 cell growth at concentrations of 25 nM and above (p < 0.01). Lovastatin added to mitomycin-C-treated cells resulted in a significant adjuvant effect, with cell growth slowed by an additional 20-30% by 1 microM lovastatin and by an additional 43-63% by 5 microM lovastatin, compared to mitomycin-C alone (p < 0.01). Lovastatin-treated cells also exhibited decreased adherence to substrate (p < 0.05). CONCLUSIONS:Lovastatin is effective alone and as an adjuvant to mitomycin-C in slowing the growth of HTC-4 cells. These in vitro results support further investigation of lovastatin as an adjuvant chemotherapeutic agent in animal models.