Mechanism studies on anticancer effects of nature compounds in human breast cancer cells

• Main Authors: Jia-Ni Lin, 林佳霓
• Other Authors: Sheng-Chu Kuo
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/4f8du7

博士 === 中國醫藥大學 === 癌症生物與藥物研發博士學位學程 === 102 === PART I: Yellow camellia, with its golden-yellow flowers, is rare in the world. Most studies of yellow camellia have focused on its ornamental properties; however, there were fewer published studies on its medical values. The purpose of this study was to define the chemical constituents and the biological potential of the water extract of leaves in six species of yellow camellia. Our data showed that Camellia murauchii had significantly higher total catechins and total polyphenol content than others; C. euphlebia had the highest total amino acids and GABA. Our results indicated that C. tunghinensis exhibited the highest free radical scavenging capacity and showed potent anticancer activities. C. nitidissima had stronger inhibitory effect than other species on fatty acid synthesis. In addition, active compounds were detected using liquid chromatography tandem mass spectrometry (LC/MS/MS). In addition to catechins, 3-p-coumaroylquinic acid, kamepferol-3-O-glucoside and quercetin-3-O-glucoside were found in C. tunghinensis. Taken together, yellow camellias possess biological activity and worthy of continued study. PART II: The major forms of curcuminoids found in turmeric are curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Curcuminoids, the yellow pigments in curry spice, show the maximum absorption wavelength near blue light. However, the signal transduction cascades involved in curcuminoids-PDT induced cell death on breast cancer cells still remain unclear. Photodynamic therapy (PDT) has been developed as a therapeutic modality, which could induce cell death via the formation of reactive oxygen species (ROS) under illumination with light. Here we found that curcuminoids-PDT significantly inhibited cell viability in breast cancer cell lines; especially DMC-PDT has the highest anti-proliferative effect. A comprehensive analysis of cell response to DMC-PDT showed that autophagy was an early event and apoptosis was a late event. The generation of ROS by exciting the photosensitizer in PDT can activate the mitogen-activated protein kinase (MAPK) pathway. Pre-treatment with a singlet oxygen scavenger or a JNK inhibitor in DMC-PDT resulted in the reversion of cell viability, reduced the levels of LC3-II and cleaved PARP. Interestingly, our study found that the inhibition of AMPK enhanced DMC-PDT mediated cytotoxicity and apoptosis. These results indicate that DMC may be considered as a new photosensitizer in PDT for cancer treatment.