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http://hdl.handle.net/10267/33628
Title: | PKC activators PMA and AD 198: Functional Differences Due to Localization |
Authors: | Barham, Whitney Jo |
Keywords: | Honors papers;Text;Chemistry, Department of |
Issue Date: | May-2008 |
Abstract: | Protein kinase C (PKC) is a family of serine/threonine kinases involved in numerous cell signaling pathways including the regulation of cell proliferation, differentiation and apoptosis. Because of this, the PKC family is a very attractive target for anti-cancer therapeutic drugs. In this project, two PKC binding agents were analyzed: the phorbol ester PMA (phorbol-12-myristate-13-acetate) and the anthracycline Nbenzyladraimycin-14-valerate (AD 198). PMA and AD 198 are similar in their binding to PKC (the C1b domain), their cardio protective properties, and their ability to induce apoptosis in several mammalian cell lines when administered at certain doses. The two agents differ in their localization, among other things. PMA is found throughout the cell, whereas AD 198 is confined to the cytoplasm and can not enter the nucleus. PMA promotes differentiation in K562 chronic myeloid leukemia cells when administered at non-cytotoxic doses. Results indicate that AD 198 does not induce differentiation as PMA does due to its inability to translocate PKC e to the nuclear membrane and its inability to activate PKC a and its signaling pathway. These results suggest that differential cellular effects can be achieved by selective activation of PKC isoforms using PKC activating agents that localize differently within the same cell. Localizing the drug to the cytoplasm effectively limits its function, thereby creating a more targeted agent with more useful properties in drug therapy. |
URI: | http://hdl.handle.net/10267/33628 |
Appears in Collections: | Honors Papers |
Files in This Item:
File | Description | Size | Format | |
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Final_paper_printed version.pdf | 464.03 kB | Adobe PDF | View/Open |
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