Killing of cancer cells through the use of eukaryotic expression vectors harbouring genes encoding nucleases and ribonuclease inhibitor

Abstract

Cancer gene therapy vectors are promising tools for killing cancer cells with the purpose of eradicating malignant tumours entirely. Different delivery methods of vectors into the cancer cells, including both non-viral and viral, as well as promoters for the targeted expression of genes encoding anticancer proteins were developed for effective and selective killing of cancer cells without harming healthy cells. Many vectors have been created to kill cancer cells, and some vectors suppress malignant tumours with high efficiency. This review is focused on vectors bearing genes for nucleases such as deoxyribonucleases (caspase-activated DNase, deoxyribonuclease I-like 3, endonuclease G) and ribonucleases (human polynucleotide phosphorylase, ribonuclease L, α-sarcin, barnase), as well as vectors harbouring gene encoding ribonuclease inhibitor. The data concerning the functionality and the efficacy of such vectors are presented.

Nuclear endonuclease G controls cell proliferation in ovarian cancer

“…EndoG is not only a DNA-cleaving nuclease and a cell death effector but is also a multifunctional protein modulated by intracellular ROS dynamics During the two decades since EndoG was shown to be a cell death effector in C. elegans and mice, most studies have focused on inducing EndoG activity to kill cancer cells [20,21,27] or blocking its activity to induce cytoprotection [28,29]. In this classical view, EndoG is primarily localized in mitochondria during translation and translocates to the nucleus upon apoptotic insult.…”

Barnase-Barstar Pair: Contemporary Application in Cancer Research and Nanotechnology

“…Ribonucleases are promising agents for use in anticancer therapy, as the production of RNases in the cytoplasm of eukaryotic cells leads to cell death via an apoptosis-mediated pathway [37]. Different delivery methods and promoters have been used to provide tumor-specific expression of ribonucleases, which is summarized in the recent work by E. Glinka [28]. To date, barnase has not been used directly in cancer gene therapy, but the successful use of barnase in specific cell ablation experiments shows a high potential of this enzyme for therapy.…”

“…The cloning of barstar and encoding of both barstar and barnase on a single plasmid enabled the production of active barnase in Escherichia coli [13]. From that time the barnase and its molecular twin Binase were used in numerous applications including folding studies [14,15], enzymatic activity investigation [16], protein-protein interactions investigation [17,18], positive selection of cloned inserts [19,20], providing male and female sterility in plants [21,22], crop defense system construction [23], specific cell depletion [24], virus elimination [25][26][27], and cancer cell killing [28][29][30][31].…”

Ribonucleases. Possible New Approach in Cancer Therapy

“…Today, several RNases allocated as possible candidates for anticancer agents [5][6][7][8][9]. The interferon (IFN) antiviral investigations and prostate cancer genetics have merged on a single-strand specific, regulated endoribonuclease.…”