| Summary: | 博士 === 國立臺灣大學 === 藥理學研究所 === 103 === According to Health Promotion Administration, Ministry of Health and Welfare in Taiwan, cancer has been the first place of ten leading deaths. Breast and ovarian cancer are the fourth and eighth common type in female and often seen in cancer-related death in Taiwan. In order to cure cancer efficaciously, anticancer drugs development is an important issue in cancer therapy. In this thesis, the anticancer mechanisms of moscatilin which is isolated from the stem of the orchid Dendrobriumloddigesii and MT-4 were examined in human breast cancer and ovarian cancer, respectively.
In the first part of the thesis, we evaluated the mechanism of moscatilin in suppressing the migration and metastasis of human breast cancer MDA-MB-231 cells. Transcriptional factors inducing epithelial–mesenchymal transition (EMT), such as Twist, Snail, and Akt, plays important roles in cell migration and cancer metastasis.Moscatilin inhibited the mRNA and protein expression of Twist, but not that of Snail, and subsequently inhibited N-cadherin expression. These results indicated that moscatilin inhibited migration via Akt- and Twist-dependent pathways; this finding was consistent with moscatilin’s antimetastatic activity in vivo. Therefore, moscatilin may be an effective compound for the prevention of human breast cancer metastasis.
In the second part of thesis, we evaluated the activity of MT-4 in vitro and in vivo xenograft assays.We found that p38 MAPK pathway activation was involved in MT-4-induced apoptosis. Most importantly, MT-4 also decreased heat shock protein27 expression and reduced its interaction with caspase-3, which inured cancer cells to chemotherapy resistance. These findings indicate that MT-4 could be a potential lead compound for the treatment of multidrug-resistant ovarian cancer.
Take together, our results demonstrated that moscatilin and MT-4 have unique properties and may be a potential and promising anti-cancer therapeutic option.
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