| Summary: | 博士 === 國立臺灣大學 === 生化科技學系 === 107 === Antrodia cinnamomea (also known as Antrodia camphorata), famed as “the ruby of the forest” in Taiwan, is a rare mushroom that grows only on the native Taiwanese tree Cinnamomum kanehirai. A. cinnamomea has been used in traditional medicine for hundreds of years to treat discomforts caused by alcohol consumption, diarrhoea, and hypertension. Several researchers have reported on the different biological activities of A. cinnamomea, such as anti-inflammatory and immunomodulatory effects, hepatoprotective activities, antioxidant activities, and anticancer activities. We wanted to uncover novel mechanisms of A. cinnamomea in colorectal cancer. The aims in chapter 1 were to examine whether A. cinnamomea can help fight against colorectal cancer and identify the molecular mechanisms underlying its anticancer activity. A. cinnamomea extracts showed cytotoxicity on HCT116, HT29, SW480, Caco-2 and, Colo205 colorectal cancer cells. Whole-genome expression profiling of A. cinnamomea extracts in HCT116 cells was performed. A. cinnamomea extracts upregulated the expression of the endoplasmic reticulum stress marker CHOP and its downstream gene TRB3. Moreover, dephosphorylation of Akt and mTOR as well as autophagic cell death were observed. Gene expression and autophagic cell death were reversed by the knockdown of CHOP and TRB3. Finally, we demonstrated that A. cinnamomea extracts significantly suppressed HCT116 tumour growth in nude mice. The focus of chapter 2 is white A. cinnamomea. The white variant of A. cinnamomea was observed in natural environments. However, white A. cinnamomea grew slower than A. cinnamomea. The pharmacological activity of white A. cinnamomea still remains unknown. The aims in this part were to identify the white A. cinnamomea strain, increase the total yield of white A. cinnamomea and examine whether white A. cinnamomea can help fight against cancer. The ribosomal DNA sequence data of A. cinnamomea and white A. cinnamomea suggested that the two strains used in this study are of the same species, A. cinnamomea. The special culture media composition, mPDA+mMEA, significantly increased the average weight of white A. cinnamomea by 28%. All of the stimuli, namely low-temperature stimulus, wound treatment, and light stimulus, can improve the ethanol extraction rate and wound treatment also increased the average weight of white A. cinnamomea. The HPLC chemical fingerprinting revealed that the chemical composition of A. cinnamomea and white A. cinnamomea are different, they may have significantly different biological actions and activities. Both two strains of A. cinnamomea have anticancer effects on five cancer cell lines. White A. cinnamomea even showed stronger cytotoxicity than A. cinnamomea in Huh7 and A549 cancer cells. Our findings suggest that autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway may represent a new mechanism of anti-colorectal cancer action by A. cinnamomea. Our data also proved that white A. cinnamomea belongs to A. cinnamomea, provided an optimized culture condition of white A. cinnamomea, and suggested that white A. cinnamomea is a new potential anticancer drug. In chapter 3, we introduced and compared the traits of different artificial culture methods. From this study, we believe that A. cinnamomea possess strong capability in pharmaceutical drug development.
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