The enhanced effect of phytochemicals on the growth inhibition of trichostatin A in A549 cells

• Main Authors: Kai-Yong, 陳開湧
• Other Authors: 葉姝蘭
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/58600726765739485758

碩士 === 中山醫學大學 === 營養學研究所 === 95 === Trichostatin A (TSA), a compound interferes with the acetylation/deactylation pattern of histones, is known to cause growth arrest and apoptosis induction of various cancer cells. However, the side-effects may limit its use in anticancer chemotherapy. In the present study, employing a human lung carcinoma cell line, A549 cells, we first examined whether 10μM of genistein,daidzein, β-carotene, retinoic acid or α-tocopherol, which are phytochemicals or nutrients with potential chemopreventive effect, enhance the suppressed effect of TSA on cell growth. As expected, TSA induced A549 cells growth arrest or death in a dose-dependent manner. Since TSA at 100 ng/mL strongly induce cell death, we used lower doses of TSA to examine the combinative effect of TSA with test compounds. Incubated with A549 cells for 72 h, genistein, daidzein, and β-carotene significantly enhanced the growth-suppressed effect of 50 ng/mL TSA (TSA50) in an order G≒ BC > D, while themselves did not affect cell growth. Retinoic acid and α-tocopherol had no effect. Furthermore, flow cytometric analysis revealed that G and BC significantly increased the apoptosis of A549 cells induced by TSA50. D also slightly increased TSA-induced apoptosis, but the effect was not significant. All G, BC and D significantly increased TSA50-induced acetyl-histone H3 expression as incubated with A549 cells for 24 h. In addition, G and BC significantly increased the expression of p53, a transcriptional controller of many pro-apoptotic genes, than TSA alone at 12 h. However, only G+TSA50 significantly increased the activity of caspase-3 at 24 h as compared with TSA50 alone. These results suggest that the mechanisms underling the enhancing effects of G , BC, and D on the cell growth-inhibiting effect of TSA may be associated with the modulation of histone H3 acetylation, the expression of p53, and the activity of caspase-3, however, they should be not completely the same. Further studies are warranted to investigate the precise mechanisms and the significance of these findings in vivo.