Ganoderma lucidum is one of most popular medicinal mushrooms in oriental countries. The medicinal properties of Ganoderma lucidum in the treatment of various diseases have been documented for hundreds of years. In recent years, more and more attentions are paid on the studies of the action mechanisms of bioactive compounds purified from this mushroom. / In conclusion, the Ganoderma steroids EP and 9(11)-DHEP can induce caspase-dependent apoptosis in susceptible cancer cells via the mitochondria-mediated pathway. In vitro and in vivo studies suggested that these two fungal steroids have the potential to be used as natural chemopreventive agents. / Keywords: Ergosterol peroxide, 9(11)-dehydroergosterol peroxide, Ganoderma lucidum, Mycelia, Antitumor activity, Apoptosis / The antiproliferative activities of EP and 9(11)-DHEP were studied by flow cytometry. Exposure of cancer cells with these two fungal steroids resulted in an accumulation of cell population at the subG1 phase in a dosage- and time-dependent manner, indicating the induction of apoptotic cell death. Morphological apoptotic changes in HepG2 cells and A375 cells were observed using TUNEL assay and Annexin-V-FLUOS assay. The signaling pathway in apoptotic cell death induced by EP and 9(11)-DHEP involved the activation of caspase 3, 7 and 9, followed by the cleavage of PARP. In Colo201 cells, a change in the ratio of expression levels of Bcl-2/Bax was observed in cells treated with EP and 9(11)-DHEP. In A375 cells, exposure to EP and 9(11)-DHEP resulted in the release of mitochondrial cytochrome c, the down-regulation of Mcl-1 and a slight up-regulation of Bak in a dosage-dependent manner. All these results indicated that apoptotic cell death in susceptible cancer cells induced by EP and 9(11)-DHEP was via the mitochondria-mediated pathway. / The in vivo antitumor activity of EP was demonstrated. EP was shown to suppress the growth of A375 cells in a nude mice xenograft model. Further studies showed that EP induced the cleavage of PARP and enhanced the total caspase 7 gene expression in the tumor cells. / Triterpenes and steroids are two important classes of Ganoderma lucidum metabolites of low molecular mass that are responsible for the antitumor activities of the mushroom. In this study, two fungal steroids, namely, 5alpha,8alpha-epidioxy-22E-ergosta-6,22-dien-3beta-ol (ergosterol peroxide (EP)) and 5alpha,8alpha-epidioxy-22E-ergosta-6,9(11),22-trien-3beta-ol (9,11-dehydroergosterol peroxide (9(11)-DHEP)) were purified from the mycelia of Ganoderma lucidum grown under submerged culture using activity-guided purification procedures against human breast adenocarcinoma MCF-7 cells. In addition to MCF-7 cells, both of these two fungal steroids showed antiproliferative activities against other human cancer cells including hepatocellular carcinoma HepG2 cells, colorectal carcinoma Colo201 cells, esophageal squamous carcinoma KYSE cells and malignant melanoma A375 cells. However, EP and 9(11)-DHEP were less toxic to MCF-10-2A, non-tumorigenic human epithelial cells, and the normal human skin fibroblast Hs68 cells. / Zheng, Lin. / Adviser: Y. S. Wong. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0253. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 153-176). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344380 |
| Date | January 2009 |
| Contributors | Zheng, Lin, Chinese University of Hong Kong Graduate School. Division of Biology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xix, 189 leaves : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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