Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia Cinnamomea, Induces Mitochondria and ER Stress-mediated Apoptosis in Human Hepatoma Cells
碩士 === 國立臺灣大學 === 食品科技研究所 === 101 === Liver cancer is the second leading cause of cancer deaths in Taiwan as per the 2012 statistics, and ranks the fourth in cancer related mortality in the world. Hence there is a need to focus more on hepato protective foods maintain a healthy liver is a big issue...
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ndltd-TW-101NTU052520152015-10-13T23:05:29Z http://ndltd.ncl.edu.tw/handle/73260156350501100700 Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia Cinnamomea, Induces Mitochondria and ER Stress-mediated Apoptosis in Human Hepatoma Cells 椴木栽培牛樟芝子實體中三萜類活性成分 Antcin K藉由誘導人類肝癌細胞粒線體及內質網壓力調節之細胞凋亡達到抑癌效果 Chiao-Yi Lai 賴巧憶 碩士 國立臺灣大學 食品科技研究所 101 Liver cancer is the second leading cause of cancer deaths in Taiwan as per the 2012 statistics, and ranks the fourth in cancer related mortality in the world. Hence there is a need to focus more on hepato protective foods maintain a healthy liver is a big issue in Taiwan. Recent researches have shown that Antrodia cinnamomea, a Taiwan-specific medicinal mushroom, can manipulate biological activities, include hepatoprotection, anti-inflammation, anti-HBV activity, anticancer activity, etc. The active constituents include polysaccharides, triterpenoids, steroids, etc., and among these, m whose triterpenoids are the most prominent because of their potent anticancer effects. In this study, the anti-liver cancer activity and molecular mechanisms of antcin K, the most abundant ergostsne triterpenoid from the fruiting bodies of basswood cultivated Antrodia cinnamomea was investigated using the human hepatoma Hep 3B cells. The results show that antcin K effectively reduced Hep 3B cell viability within 48 hours. In addition, antcin K induced phosphatidylserine exposure, chromatin condensation, DNA damage, but not significantly increasing autophagosome content or causing cell expansion and cell lysis. So the principal mode of Hep 3B cell death induced by antcin K was apoptosis, rather than autophagy or necrosis. In depth investigation for the molecular mechanisms, revealed that antcin K firstly promoted ROS generation and ATP depletion, lead to ER stress, followed by CHOP expression, down-regulated Bcl-xL and activated Bax/Bak channel to promote intra-cellular calcium ion release from the endoplasmic reticulum then uptake into the mitochondria, resulting in mitochondrial membrane permeability changes. After losing of mitochondrial membrane potential, the apoptosis related factors were released, including HtrA2/Omi, AIF, Endo-G and cytochrome c, the cytochrome c activated the caspase-9, caspase-3, and cut downstream protein PARP, ultimately leading to cell apoptosis. These results suggested that antcin K induced endoplasmic reticulum stress and mitochondria-mediated apoptosis in human hepatoma cells. Coupled with these findings, antcin K has the potential to be complementary agent in liver cancer therapy. Lee-Yan Sheen 沈立言 2013 學位論文 ; thesis 137 zh-TW |
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碩士 === 國立臺灣大學 === 食品科技研究所 === 101 === Liver cancer is the second leading cause of cancer deaths in Taiwan as per the 2012 statistics, and ranks the fourth in cancer related mortality in the world. Hence there is a need to focus more on hepato protective foods maintain a healthy liver is a big issue in Taiwan. Recent researches have shown that Antrodia cinnamomea, a Taiwan-specific medicinal mushroom, can manipulate biological activities, include hepatoprotection, anti-inflammation, anti-HBV activity, anticancer activity, etc. The active constituents include polysaccharides, triterpenoids, steroids, etc., and among these, m whose triterpenoids are the most prominent because of their potent anticancer effects. In this study, the anti-liver cancer activity and molecular mechanisms of antcin K, the most abundant ergostsne triterpenoid from the fruiting bodies of basswood cultivated Antrodia cinnamomea was investigated using the human hepatoma Hep 3B cells. The results show that antcin K effectively reduced Hep 3B cell viability within 48 hours. In addition, antcin K induced phosphatidylserine exposure, chromatin condensation, DNA damage, but not significantly increasing autophagosome content or causing cell expansion and cell lysis. So the principal mode of Hep 3B cell death induced by antcin K was apoptosis, rather than autophagy or necrosis. In depth investigation for the molecular mechanisms, revealed that antcin K firstly promoted ROS generation and ATP depletion, lead to ER stress, followed by CHOP expression, down-regulated Bcl-xL and activated Bax/Bak channel to promote intra-cellular calcium ion release from the endoplasmic reticulum then uptake into the mitochondria, resulting in mitochondrial membrane permeability changes. After losing of mitochondrial membrane potential, the apoptosis related factors were released, including HtrA2/Omi, AIF, Endo-G and cytochrome c, the cytochrome c activated the caspase-9, caspase-3, and cut downstream protein PARP, ultimately leading to cell apoptosis. These results suggested that antcin K induced endoplasmic reticulum stress and mitochondria-mediated apoptosis in human hepatoma cells. Coupled with these findings, antcin K has the potential to be complementary agent in liver cancer therapy.
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author2 |
Lee-Yan Sheen |
author_facet |
Lee-Yan Sheen Chiao-Yi Lai 賴巧憶 |
author |
Chiao-Yi Lai 賴巧憶 |
spellingShingle |
Chiao-Yi Lai 賴巧憶 Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia Cinnamomea, Induces Mitochondria and ER Stress-mediated Apoptosis in Human Hepatoma Cells |
author_sort |
Chiao-Yi Lai |
title |
Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia Cinnamomea, Induces Mitochondria and ER Stress-mediated Apoptosis in Human Hepatoma Cells |
title_short |
Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia Cinnamomea, Induces Mitochondria and ER Stress-mediated Apoptosis in Human Hepatoma Cells |
title_full |
Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia Cinnamomea, Induces Mitochondria and ER Stress-mediated Apoptosis in Human Hepatoma Cells |
title_fullStr |
Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia Cinnamomea, Induces Mitochondria and ER Stress-mediated Apoptosis in Human Hepatoma Cells |
title_full_unstemmed |
Antcin K, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia Cinnamomea, Induces Mitochondria and ER Stress-mediated Apoptosis in Human Hepatoma Cells |
title_sort |
antcin k, an active triterpenoid from the fruiting bodies of basswood cultivated antrodia cinnamomea, induces mitochondria and er stress-mediated apoptosis in human hepatoma cells |
publishDate |
2013 |
url |
http://ndltd.ncl.edu.tw/handle/73260156350501100700 |
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