Published in:
01-02-2010 | Original Contribution
Genistein and β-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells
Published in: European Journal of Nutrition | Issue 1/2010
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Background
The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy and decreasing the toxicity of chemotherapy. However, whether nutritional factors enhance the effect of trichostatin A (TSA), a novel anti-cancer drug, is unclear.
Aim
We investigated the individual enhancing effect and its possible mechanisms of genistein, daidzein, β-carotene, retinoic acid, and α-tocopherol on the cell-growth-inhibitory effect of TSA in a human lung carcinoma cell line, A549.
Methods
A549 cells were incubated with TSA (50 ng/mL) alone or in combination with the various nutritional factors for various times, and cell growth was measured. IMR90 cells, human lung fibroblasts, were also incubated with TSA alone or in combination with genistein or β-carotene to determine the selectivity of these treatments. In addition, we studied effects on the cell cycle, caspase-3 activity, and DNA damage (by comet assay) in A549 cells.
Results
After treatment for 72 h, 10-μM genistein or β-carotene significantly enhanced the growth-inhibitory effect of TSA in A549 cells. Daidzein, retinoic acid, and α-tocopherol at the same concentration had no significant effect. However, genistein and β-carotene failed to enhance the cell-growth-arrest effect of TSA in IMR90 cells. Flow cytometric analysis showed that both genistein and β-carotene significantly increased the TSA-induced apoptosis in A549 cells. Genistein significantly enhanced TSA-induced caspase-3 activity in A549 cells by 34% at 24 h, and the caspase-3 inhibitor partly inhibited the enhancing effect of genistein on TSA-induced apoptosis. β-Carotene did not significantly affect TSA-induced caspase-3 activity. However, β-carotene rather than genistein enhanced TSA-induced DNA damage.
Conclusions
Genistein and β-carotene enhance the cell-growth-arrest effect of TSA on A549 cells. Genistein exerts its effect, at least partly, by increasing caspase-3 activity; whereas β-carotene may enhance TSA-induced cell death mainly through a caspase-3-independent pathway.