Cytotoxic activity of Fagonia cretica against human breast cancer cells

In many parts of the world, plants are directly utilised for their medicinal properties. Traditional medicine from Pakistan, India and the Far East is well documented and its history is embedded in folklore. It has been documented that an aqueous extract of the desert shrub, Fagonia cretica, is a popular treatment for breast cancer in Pakistan. The administration of an aqueous extract of Fagonia cretica is reported effective at reducing tumour size and improving the quality of life of breast cancer patients, is well tolerated and does not exhibit adverse effects like vomiting, diarrhoea or alopecia which are common side effects of standard cytotoxic therapy. In the past, many pharmacologically active and chemotherapeutic compounds have been isolated from plants which subsequently have proven to be successful in clinical trials and been used as primary compounds in therapeutic regimes. Fagonia cretica has historical use as a treatment for breast cancer, yet there is little scientific evidence which shows chemotherapeutic potential towards breast tumours. Preparation and analysis of an aqueous extract of Fagonia cretica may reveal novel chemotherapeutic agents that can be used to effectively target cancer cells. An understanding of the mechanism of any activity may improve our understanding of cancer cell biology and reveal novel therapeutic targets. This thesis describes for the first time that an aqueous extract of Fagonia cretica shows potent in vitro cytotoxic activity towards breast cancer epithelial cell lines which was not seen towards normal mammary epithelial cells. Elucidation and characterisation of the cytotoxic mechanism was undertaken by analysing DNA damage, cell cycle status, apoptosis, metabolic state and expression of transcription factors and their targets. Finally, methods for the isolation and identification of active compound(s) were developed using various chromatographic techniques. An aqueous extract of Fagonia cretica was able to reduce cell viability significantly in two phenotypically different breast cancer cell lines (MCF-7 and MDA-MB-231). This activity was markedly reduced in normal mammary epithelial cells (HMEpC). Further investigation into the mode of action revealed that extract treatment induced cell cycle arrest and apoptosis in both MCF-7 and MDA-MB-231 cell lines. This coincided with the formation of DNA double stranded breaks and the DNA repair marker ?-H2AX. In MCF-7 cells, ATM/ATR activation resulted in increased p53 expression and of its transcriptional targets p21 and bax, suggesting a role for a p53-mediated response. Furthermore, inhibition of extract-induced p53 expression with siRNA reduced the cytotoxic effect against MCF-7 cells. Extract treatment was also associated with increased FOXO3a expression in MCF-7 and MDA-MB-231 cells. In the absence of functional p53, siRNA knockdown of extract-induced FOXO3a expression was completely abrogated, suggesting that FOXO3a plays a vital role in extract-induced cytotoxicity. Isolation and characterisation of the active compound(s) within the extract was attempted using liquid chromatography and mass spectrometry in conjunction with a cell viability assay. Multiple fractionations generated an active fraction that contained four major compounds as detected by mass spectrometry. However, none of these compounds were identified structurally or chemically due to constraints within the methodology.

Computational methods for traditional Chinese medicine:a survey

Traditional Chinese Medicine (TCM) has been actively researched through various approaches, including computational techniques. A review on basic elements of TCM is provided to illuminate various challenges and progresses in its study using computational methods. Information on various TCM formulations, in particular resources on databases of TCM formulations and their integration to Western medicine, are analyzed in several facets, such as TCM classifications, types of databases, and mining tools. Aspects of computational TCM diagnosis, namely inspection, auscultation, pulse analysis as well as TCM expert systems are reviewed in term of their benefits and drawbacks. Various approaches on exploring relationships among TCM components and finding genes/proteins relating to TCM symptom complex are also studied. This survey provides a summary on the advance of computational approaches for TCM and will be useful for future knowledge discovery in this area. © 2007 Elsevier Ireland Ltd. All rights reserved.

The impact of the post-1993 economic reforms on Chinese state-owned enterprises:evidence from the electronics industry

Since 1979, China has embarked on a series of economic reform programmes, leading its socialist economy away from a Soviet planning model towards a much greater reliance on the market. In the course of the last twenty years, the Chinese economy has enjoyed a phenomenally high economic growth rate. However, earlier research suggests that Chinese state-owned enterprises remain a financial 'black hole' for the Chinese economy, in spite of various enterprise reform measures. This thesis tries to assess the impact of the reforms after 1993, especially the so-called Modern Enterprise System, on the behaviour and management practices of state firms. The central research question is whether the new rounds of economic reform have changed state firms into commercial entities operating according to market signals, as intended. In order to explore this question, an institutional approach is employed. More specifically, the thesis examines how the behaviour and management practices of state enterprises have changed with changes in the institutional environmental resulting from the introduction of new reform measures and especially the MES. The main evidence used in this research comes from the Chinese electronics industry (CEI). Non-state firms, namely collectives and joint ventures, are involved in the study to provide a benchmark against which changes in the behaviour of state firms in the mid and late 1990s are compared. A comparative statistical analysis shows that state-owned firms, both traditional and corporatised ones, still lag behind collectives and joint ventures in terms of both labour and total factor productivity. The further empirical work of this research consists of a questionnaire survey and case studies that are based on interviews with senior managers of 17 firms in the CEI. The findings of these analyses suggest that there has been little fundamental change in the behaviour pattern of state firms in the 1990s, despite the introduction of the Modern Enterprise System, and that the economic reforms after 1993 so far seem to have failed to transform the state firms into commercial entities operating according to market signals.