Document Type
Honors Thesis
Abstract
The solution to cancer has been elusive due to the toxicity inadvertently involved with healthy cells and the increasing level of resistance to current chemotherapeutics. This includes the gold standard cancer therapeutics such as the platinum based complex, cisplatin. As a result, other alternative metal pharmaceuticals, such as ruthenium-based complexes, have been sought after due to their low cytotoxicity profile towards healthy cells and increased cytotoxicity towards malignant cells. Previous in cellulo experiments showed the ruthenium polypyridyl complexes [(phen)2Ru(tatpp)]Cl2 (MP2+) and [(phen)2Ru(tatpp)Ru(phen)2]Cl4 (P4+) accumulating in the mitochondria. Here the complexes were tested to see if both MP2+ and P4+ are mitochondrial toxins due to their accumulation in the mitochondria and whether the mitochondria is a main site of action of one or both complexes. In addition the investigation included insight into interplay between the complexes and the Warburg effect in galactose based medium.. The non -small cell lung cancer cell line H358 was chosen due to its deficiency in the tumor suppressor gene p53, inevitably negating any effects of p53 mediated apoptosis by certain mitochondrial drugs. The Promega Mitochondrial ToxGlo multiplex assay was used to measure the degree of membrane permeability and adenosine triphosphate (ATP) synthesis decoupling from ATP synthase, resulting in either apoptosis or necrosis. Due to both P4+ and MP2+ currently being filed for a patent and current data unpublished, only the controls Oligomycin, digitonin, and ruthenium polypyridyl complex DIP were discussed. Oligomycin was replicated as a mitochondrial poison, digitonin as a necrotic agent, and DIP as a weak mitochondrial poison. All three matched their respective toxicity profiles seen in previous experiments validating the experiment as well as helping to elucidate a deeper outlook of the mechanism of action of P4+ and MP2+.
Publication Date
5-1-2016
Language
English
License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Mohamedi, Ali, "DETERMINATION OF MITOCHONDRIAL TOXICITY AND POTENTIAL APOPTOTIC PATHWAY OF RUTHENIUM POLYPYRIDYL COMPLEXES [(phen)2Ru(tatpp)]Cl2 AND [(phen)2Ru(tatpp)Ru(phen)2]Cl4" (2016). 2016 Spring Honors Capstone Projects. 16.
https://mavmatrix.uta.edu/honors_spring2016/16