Fish Oil Enhances the Antiproliferative Effect of 1α,25-Dihydroxyvitamin D3 on Liver Cancer Cells

Background: Laboratory and epidemiological studies have indicated that la,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] and dietary omega 3 (omega 3)-polyunsaturated fatty acids (PUFAs) are capable of inhibiting the proliferation of various cancer cells. Materials and Methods: Human hepatoblastoma cells (HepG2) were treated with 1 alpha,25(OH)(2)D-3 and fish oil alone and in combination. Cell proliferation was measured either by the uptake of [H-3]-thymidine into DNA or by, counting the cell numbers using a hemocytometer. Results: The HepG2 cell proliferation was inhibited by 1 alpha,25(OH)(2)D-3 and fish oil in a dose-dependent manner. The lowest effective concentration of 1 alpha,25(OH)(2)D-3 was 10(-7) M and 10(-8) M using the [H-3]-thymidine incorporation method and the cell counting method, respectively. Fish oil also caused a significant inhibition in HepG2 cell proliferation at 25 mu g/mL. When HepG2 cells were treated with 1 alpha,25(OH)(2)D-3 in combination with fish oil, it was found that fish oil increased the antiproliferative effect of 1 alpha,25(OH)(2)D-3 on HepG2 cell growth compared to treatment with 1 alpha,25(OH)(2)D-3 alone. Conclusion: 1 alpha,25(OH)(2)D-3 could be used to treat hepatocellular carcinoma (HCC). However, the major side-effect of hypercalcemia limits its use. An enhanced 1 alpha,25(OH)(2)D-3-induced inhibition of HepG2 cell proliferation in the presence of PUFAs in the form of fish oil suggests that a lower concentration of 1 alpha,25(OH)(2)D-3 could be used to treat hepatocellular carcinoma in the presence of PUFAs to decrease the risk of hyperealcemia caused by high concentrations of 1 alpha,25(OH)(2)D-3.