| Summary: | 碩士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 93 === PART1
Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death in men in western world. Androgen-independent prostate cancer (AIPC), an untreatable and fatal malignancy, almost invariably develops subsequent to androgen ablation therapy in early stage prostate carcinoma. At present, there is no effective therapy for it.
The metastasis of prostate cancer to bone is associated with a substantial bone matrix turnover. Matrix metalloproteinase-9 (MMP-9) plays roles in both normal bone remodeling and invasion and metastasis of prostate cancer. Bone matrix turnover and tumor cell proliferation are linked to each other in a positive feedback cycle that can be disrupted by inhibition of MMP activity. Additionally, EGF induces MMP-9 expression in many prostate cancer cells and its cognate receptor, EGFR, is proposed to be involved in the development of androgen-independent prostate cancer (AIPC).
Penta-O-galloyl-β-D-glucose (5GG), a kind of galloylglucose, contains one glucose and esterified with five gallic acid on five hydroxyl groups of the glucose. It has been shown to exert several biological activities including anti-oxidation, induction of apoptosis and metastasis inhibition.
In this study, we demonstrated that EGF-induced MMP-9 expression was inhibited by 5GG. Subsequently, we seek to figure out the signal transduction pathways involved in 5GG-mediated MMP-9 down-regulation under EGF stimulation. We found that NF-κB nuclear translocation was reduced. Therefore, we examined the signal transduction pathways that may be involved in regulating NF-κB nuclear translocation. We found that 5GG inhibited JNK1/2 phosphorylation but maintained Akt phosphorylation with minimal effect on ERK1/2 and p38 under EGF induction. Next, we checked the phosphorylation status of EGFR. Surprisingly, we found that 5GG down-regulated not only EGFR phosphorylation but also its protein level under EGF stimulation. By using proteasome and lysosome inhibitors, we demonstrated that this phenomenon resulted from 5GG-mediated EGFR protein degradation.
Inhibition of MMP-9 and EGFR expression by 5GG may help reduce the frequency of prostate cancer bone metastasis and the development of AIPC. These findings make 5GG a therapeutic candidate for prostate cancer.
Part2
The invading foreign species in Taiwan have caused tremendous losses in agriculture and economy. They also destroy the established ecology of Taiwan. One of these invading species is the African Giant snail, which eats up new leaves and buds of the crops. Efforts have been made to prevent the spread of snails but little effect is seen. In this study, we tried to investigate the conventional, naturally degradable oil tea pomace in inhibiting the activity of snails. We found that both two kinds of oil tea pomace water extracts were capable of killing snails, causing their over-secretion of surface mucus, thus dehydrated to death. We also found that these oil tea pomace water extracts were cytotoxic only at higher doses. Finally, we examined the total amount of phenols in these oil tea pomace water extracts. We found that they didn’t contain much amount of phenols, suggesting that the molluscicidal activity of oil tea pomace water extracts was not resulted from phenols. Overall, these information provided us some insights into the molluscicidal activity of oil tea pomace. However, the exact active component in oil tea pomace water extracts remained to be clarified, one possibility was the saponins.
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