β-ionone의 인체 비소폐암세포 A-549에 대한 anti-proliferative 효과

Abstract

<TEX>${\beta}$</TEX>-Ionone의 인체 비소폐암세포 A-549 cells (human non-small lung cancer A-549 cell)에 대한 anti-proliferative effect에 관한 연구를 수행하였다. A-549 cell에 다양한 농도의 <TEX>${\beta}$</TEX>-ionone (1, 5, 10, and 15 <TEX>${\mu}M$</TEX>)을 2, 4, 6일 간 처리하고, 배양 2일에 A-549 cell의 생육억제와 관련되는 biochemical marker를 측정하였다. <TEX>${\beta}$</TEX>-Ionone은 A-549 cell 생육을 dose와 time 의존적으로 저해하였다. <TEX>${\beta}$</TEX>-Ionone 배양 2일의 <TEX>$IC_{50}$</TEX>은 5.0 <TEX>${\mu}g/ml$</TEX>이었다. <TEX>${\beta}$</TEX>-Ionone은 농도 의존적으로 apoptosis를 유도하였다. <TEX>${\beta}$</TEX>-Ionone은 p53, p21 및 Bax protein 수준을 증가시켰으나, Bcl-2 protein 발현은 억제시켰다. <TEX>${\beta}$</TEX>-ionone은 cytosol cytochrome c 함량을 증가시켰고, caspase-9과 caspase-3 효소 활성증가를 유도하였다. 또한, <TEX>${\beta}$</TEX>-ionone은 <TEX>$cPLA_2$</TEX>와 COX-2 protein level을 감소시켰다. 이와 같은 결과는 <TEX>${\beta}$</TEX>-ionone의 A-549 cell에 대한 생육억제효과는 Bax와 Bcl-2 gene 발현을 reciprocal regulation하여 유도한 apoptosis와 <TEX>$cPLA_2$</TEX> 및 COX-2 protein 발현 억제에 기인함을 의미한다. The anti-proliferative activity of <TEX>${\beta}$</TEX>-ionone was investigated on human non-small lung cancer A-549 cells (designated A-549 cells). A-549 cells were treated with various concentrations of <TEX>${\beta}$</TEX>-ionone (1, 5, 10, and 15 <TEX>${\mu}M$</TEX>) for two, four, and six days. Biochemical markers related to the growth inhibition of A-549 cells by <TEX>${\beta}$</TEX>-ionone were measured at the second day of incubation. <TEX>${\beta}$</TEX>-Ionone inhibited the growth of A-549 cells by dose-and time-dependent manners, resulting in an <TEX>$IC_{50}$</TEX> of 5.0 <TEX>${\mu}g/ml$</TEX> at the second day of incubation. <TEX>${\beta}$</TEX>-Ionone induced apoptosis by a dose-dependent manner. <TEX>${\beta}$</TEX>-Ionone increased levels of p53, p21, and Bax proteins, but suppressed expression of the Bcl-2 protein. Similarly, <TEX>${\beta}$</TEX>-ionone enhanced cytochrome c release from the mitochondria to the cytosol, and induced activation of caspase-9 and -3. Additionally, <TEX>${\beta}$</TEX>-ion-one reduced <TEX>$cPLA_2$</TEX> and COX-2 protein levels. These results suggest that the <TEX>${\beta}$</TEX>-ionone inhibits the proliferation of A-549 cells through reciprocal regulation of Bax and Bcl-2 gene expression and suppression of <TEX>$cPLA_2$</TEX> and COX-2 protein expressions.