Study of the Effects of High Dose Naringenin on Cell Apoptosis in HaCaT Human Keratinocytes

• Main Authors: Ya-Wen Lin, 林雅雯
• Other Authors: Shu-Jem Su
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/82227865467234860945

碩士 === 輔英科技大學 === 醫事技術系碩士班 === 98 === Naringenin is a plant bioflavonoid found in citrus fruits, that has anti-carcinogenic, anti-oxidative, and phytoestrogenic activities. In citrus essential oils often contain naringenin, and adds into the cosmetics, the maintenance, the whitening and the sunscreen products, but the toxic dosage of naringenin and potential underlying molecular mechanisms in the skin are unclear. Thus, the aims of this study were to examine the toxic effects of naringenin in keratinocytes, and to investigate the cellular mechanisms by which naringenin causes cytotoxicity in the cells. In the present study, we examined the effects of naringenin on the cell growth, cell cycle progression, and apoptosis induction in the human keratinocyte cell line, HaCaT. This study showed that high dose exposure was cytotoxic, but lesser doses did not cause cell death. Naringenin induced cell death by apoptosis in a dose-dependent manner, as demonstrated by the appearance of condensed chromatin, the migration of cells into the sub-G1 phase, the increase of dUTP nickend-labeling (TUNEL) positively stained cells, and the formation of nuclear DNA fragmentation. Analysis of the molecular mechanism is involved in naringenin could up-regulation of Fas, FasL, FADD and down-regulation of pro-caspase 8, pro-caspase 3, Bcl-2, and NF-κB expression. However, the expressions of TNF-α, TRADD, Bax and cytochrome C were lower or not affect. By pre-treatment with the caspase 8 inhibitor, z-IETD fmk, the cell survival significantly increased about 30 %. In addition, vimentin contributes to epithelial cell migration and adhesion is also decreased by naringenin. Taken together, these results suggested that exposure to naringenin might induce apoptosis of HaCaT cells through a FasL-dependent pathway. In the future when we will use the citrus essential oil or naringenin, these results will be an important dosage reference.