The mechanisms of phytochemicals on induction of apoptosis and anti-inflammation in vitro and in vivo

• Main Authors: You-Syuan Lai, 賴幼軒
• Other Authors: Min-Hsiung Pan
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/25183463236341624608

碩士 === 國立高雄海洋科技大學 === 水產食品科學研究所 === 95 === Polymethoxyflavonoids (PMFs) have been particular interest because many of these flavonoids exhibit a broad spectrum of biological activity, including anti-inflammatory, anti-carcinogenic, anti-tumor and anti-oxidant properties. In the present study, to evaluate the number and position of hydroxyl groups on polymethoxyflavonoids on the associated biological properties in vitro, the cell viability, apoptotic ratio, cell cycle distribution of several human cancer cell lines were determined. The results showed that 5-hydroxy-3, 6, 7, 8, 3’, 4’-hexamethoxyflavone (5-OH-HxMF) was effective as an anti-proliferative agent of human cancer cells and induction of apoptosis in HL-60 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). ROS generation occurred in the early stages of 5-OH-HxMF-induced apoptosis, subsequently cytochrome c release, caspase activation, DNA fragmentation and induced the degradation of DNA fragmentation factor (DFF-45) and poly- (ADP-ribose) polymerase. We also found that single breaks of DNA in 5-OH-HxMF-treated HL-60 cells, suggesting that 5-OH-HxMF-induced irreparable DNA damage, which in turn triggered the process of apoptosis. Furthermore, antioxidants such as N-acetylcysteine (NAC) and catalase (CAT) suppressed 5-OH-HxMF-induced apoptosis as well as DNA damage inducible gene 153 (GADD153) proteins in a time-dependent manner. Taken together, these results suggested that 5-OH-HxMF creates an oxidative cellular environment that induces DNA damage, and then trigger apoptosis in HL-60 cells.