It was found that narciclasine retarded the growth of human cancer cells and plant suspension cells in dose-dependent manner. The inhibitory mechanism of narciclasine was found to be apoptosis for the DNA histogram showed an apoptotic peak in narciclasine-treated A375 cancer cells. The fluorescent signal dUTP fluorescein was found in the narciclasine-treated A735 cancer cell in TUNEL assay. The Annexin-V-FLUOS stained A375 cancer cell at 24-hour treatment with no PI found. These results suggest that narciclasine triggered early apoptosis in A375 cancer cell. Immunoblot analysis of the apoptotic signalling pathway showed that narciclasine induced apoptosis through the intrinsic pathway. Narciclasine induced the cleavage of caspase-9 but not the caspase-8, which was triggered by cytochrome c release from mitochondrial intermembrane space into cytosol. The activated caspase-9 triggered caspase cascade (e.g. cleavage of caspase-3, caspase-6 and caspase-7) which induced the cleavage of PARP. / Narciclasine is an isoquinoline alkaloid extracted from the bulb of Narcissus tazetta. It shows a wide range of biological activities such as antitumour, antiviral and plant growth inhibitory activities. However, little information is available regarding such inhibitory activities. The objective of this study is to elucidate the mechanisms of the cytotoxic effects of narciclasine in different cell models. / On the other hand, narciclasine triggered programmed cell death (PCD) in plant cells as proved by the increased intensity of Evans blue in narciclasine-treated suspension cells. Fluorescent microscopy showed that narciclasine induced PCD in tobacco BY2 cell with the dUTP fluorescein stained in narciclasine-treated cell. The induction of PCD was in dose-dependent and time-dependent manner. / Proteomic studies showed that narciclasine may affect A375 cancer cell and rice meristemic cells in similar manner. Narciclasine may affect the metabolism and defence system of both A375 cancer cell and rice meristemic cells through down-regulating the expression of metabolic enzymes (e.g. triosephosphate isomerase in A375 cancer cell and fructose bisphosphate aldolase in rice root tip) and defensive proteins (e.g. peroxiredoxin in A375 cancer cell and catalase in rice root tip). Narciclasine down-regulated the heat-shock proteins (HSP) which is involved in regulating cellular homeostasis and promoting cell survival. Therefore, narciclasine reduced HSP to lower the cell survival ability and induced the caspase cascade or caspase-like activity in A375 cancer cell and rice respectively. / To summarize, narciclasine induced apoptosis in A375 cancer cell and programmed cell death in tobacco BY2 cell. / Wong, Chi Fai. / "October 2007." / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4576. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 230-255). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344149 |
| Date | January 2007 |
| Contributors | Wong, Chi Fai, 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 (xx, 255 p. : 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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