Fish oil enhances the antiproliferative effect of 1alpha,25-dihydroxyvitamin D3 on liver cancer cells.

BACKGROUND

Laboratory and epidemiological studies have indicated that 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and dietary omega 3 (omega3)-polyunsaturated fatty acids (PUFAs) are capable of inhibiting the proliferation of various cancer cells.

MATERIALS AND

METHODS

Human hepatoblastoma cells (HepG2) were treated with 1alpha,25(OH)2D3 and fish oil alone and in combination. Cell proliferation was measured either by the uptake of [3H]-thymidine into DNA or by counting the cell numbers using a hemocytometer.

RESULTS

The HepG2 cell proliferation was inhibited by 1alpha,25(OH)2D3 and fish oil in a dose-dependent manner. The lowest effective concentration of 1alpha,25(OH)2D3 was 10(-7) M and 10(-8) M using the [3H]-thymidine incorporation method and the cell counting method, respectively. Fish oil also caused a significant inhibition in HepG2 cell proliferation at 25 microg/mL. When HepG2 cells were treated with 1alpha,25(OH)2D3 in combination with fish oil, it was found that fish oil increased the antiproliferative effect of 1alpha,25(OH)2D3 on HepG2 cell growth compared to treatment with 1alpha,25(OH)2D3 alone.

CONCLUSION

1alpha,25(OH)2D3 could be used to treat hepatocellular carcinoma (HCC). However, the major side-effect of hypercalcemia limits its use. An enhanced 1alpha,25(OH)2D3-induced inhibition of HepG2 cell proliferation in the presence of PUFAs in the form of fish oil suggests that a lower concentration of 1alpha,25(OH)2D3 could be used to treat hepatocellular carcinoma in the presence of PUFAs to decrease the risk of hypercalcemia caused by high concentrations of 1alpha,25(OH)2D3.