Drug metabolism and apoptosis in HEPG2 cell line

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2017

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Rustam, Samir

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The liver is the principal site of drug metabolism. Drugs and other chemicals are all metabolized in the liver through the drug-metabolizing enzyme system. Metabolized drugs can have an effect on one another through crosstalk between drug metabolism pathways. Herbs used in folk and mainstream medicine, when taken together with drugs, can affect the rate at which drugs are processed by the liver. Salvia species are one of many herbal remedies which can be used together with prescribed drugs as part of alternative traditional medicine. Therefore, it is important to learn the effects of Salvia extracts on drug metabolism, and how it affects the metabolism of other drugs and their therapeutic ability when consumed together. Previously, we have characterized the water and methanol extracts of a Salvia species, S. absconditiflora, in our lab. In this study, we examine the effects of these extracts on gene expression of phase I and phase II enzymes by using quantitative real-time PCR panel microplates containing primers targeting these enzyme gene transcripts, and also further investigate the effects of S. absconditiflora extracts on ROS generation and the expression of genes associated with apoptosis. Web based Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for the analysis of pathway panel results. Analysis of changes in the metabolism pathways in response to S. absconditiflora extracts have revealed important ramifications for the metabolism of carcinogens and drugs involved in cancer therapy. S. absconditiflora extracts alter expression of key enzymes involved in the metabolism of carcinogens. Extracts also demonstrated the ability to affect potency and effectiveness of co-administered drugs. Further, the decrease in expression of key genes involved in apoptosis and the upregulation of genes associated with necrosis showed that inhibition of cell proliferation due to treatment is achieved by the induction of necrosis in HepG2 cells.

Subject Keywords

Cell lines., Apoptosis., Drugs

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http://etd.lib.metu.edu.tr/upload/12620748/index.pdf
https://hdl.handle.net/11511/26239

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

S. Rustam, “Drug metabolism and apoptosis in HEPG2 cell line,” M.S. - Master of Science, Middle East Technical University, 2017.