Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription
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University of Cincinnati / OhioLINK
2016
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460652655 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-ucin14606526552021-08-03T06:35:32Z Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription Thowfeik, Fathima Shazna Biochemistry Reactive Oxygen Species AML mechanism of action cytotoxicity homologous recombination HDAC8 Cancer is a major public health problem in the worldwide and second leading cause of death in the United States. The major problem in treatment of cancer is the off target cytotoxicity. Therapeutic selectivity is therefore essential. Evidence suggests that, compared to normal cells, many types of cancer cells have increased level of ROS, a condition known as oxidative stress. Acute myeloid leukemia (AML) is known to possess of elevated levels of ROS, due to the increase expression of NADPH oxidases. Therefore to enhance the selectivity towards cancer we designed and synthesized novel anti-cancer agents that are converted to reactive molecules upon oxidation by ROS. In this study I explored the possible use of reactive oxygen-activated DNA modifying (RAC) agents against AML. A key amine on the lead agent was investigated via cytotoxicity assays and was found necessary for potency. The two best compounds were screened via the NCI-60 cell panel. These two compounds had potency between 200 and 800 nM against many of the leukemia cancer cell types. Subsequent experiments explored activity against a transformed AML model that mimics the molecular signatures identified in primary AML patient samples. 2016-06-03 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460652655 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460652655 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biochemistry Reactive Oxygen Species AML mechanism of action cytotoxicity homologous recombination HDAC8 |
| spellingShingle |
Biochemistry Reactive Oxygen Species AML mechanism of action cytotoxicity homologous recombination HDAC8 Thowfeik, Fathima Shazna Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription |
| author |
Thowfeik, Fathima Shazna |
| author_facet |
Thowfeik, Fathima Shazna |
| author_sort |
Thowfeik, Fathima Shazna |
| title |
Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription |
| title_short |
Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription |
| title_full |
Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription |
| title_fullStr |
Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription |
| title_full_unstemmed |
Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription |
| title_sort |
targeting a common enemy: toxic cellular mechanism of novel anti-cancer agents that alter dna and transcription |
| publisher |
University of Cincinnati / OhioLINK |
| publishDate |
2016 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460652655 |
| work_keys_str_mv |
AT thowfeikfathimashazna targetingacommonenemytoxiccellularmechanismofnovelanticanceragentsthatalterdnaandtranscription |
| _version_ |
1719439822004682752 |