The study of cationic amphiphilic peptides with anti-cancer selective toxicity
The exposure of organisms to environmental stresses and pathogens results in rapid activation of a range of defensive pathways that act as part of the innate immune system. The most common innate immunity response is the activation of cationic amphiphilic peptides in response to microbial infection. Moreover, cationic amphiphilic peptides possess desirable attributes for the pharmaceutical development of cancer-selective drugs. They selectively and rapidly kill cancer cells without killing normal mammalian cells and have a broad spectrum of mechanisms of action. The aim of this exploratory study was to screen for cationic amphiphilic peptides with anti-proliferative activity that is induced by genotoxicity. GeneFishing® technology, 2-D gel analysis and bioassays were used to identify and analyse molecules induced in response to genotoxic stress in an embryonic cell line originating from the dung beetle Euoniticellus intermedius. Bioassay results revealed that the cell line has constitutive expression of probable cationic amphiphilic proteins that are further induced by camptothecin treatment. GeneFishing® and 2-D gel analysis showed changes in gene expression at both transcriptional and translational levels, respectively. Overall, the study failed to identify the involvement or induction of cationic amphiphilic peptides in response to genotoxic stress. However, gene expression analyses revealed changes in the expression of classes of proteins involved in stress response, oxidative phosphorylation, mitochondrial maintenance, protein translation, cytoskeletal proteins and immunophilins. The results show that the cell line constitutively expresses probable cationic amphiphilic peptides which are further induced by camptothecin.
A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. Johannesburg, 2014.