Cancer Targeting Activity of Salmonella Invasion Protein A

Overview

Objectives/Goals Due to the fact that current conventional cancer treatments, such as chemotherapy and radiation therapy, lack specificity, the development of new forms of therapy is essential to decreasing negative impacts of the treatment on patients. Past research shows that Salmonella typhimurium is able to affect metastases and also preferentially colonize 2,000-fold more in tumors, than in liver, spleen, lung, heart, and skin. However, the precise mechanisms of the attractive interaction between bacteria and cancer cells are still unknown. In this research, Salmonella Invasion Protein A (SipA), known to change actin filament activity in the host cell, was tested for its potential role in cancer specific drug delivery. Methods/Materials In combination with SipA, a DNA restriction endonuclease (RE) fused with nuclear localization sequences (RE-NLS) was used as the toxic therapeutic agent. The NLS was hypothesized to deliver the RE-NLS fusion protein to the nucleus of the cancer cells, where the restriction enzyme would cut the cancer cell's genomic DNA and kill the cell. SipA and RE-NLS proteins were mixed with a protein transfection agent to initiate intracellular delivery of the proteins into normal and lung cancer cells from humans and mice. Results Toxicity assays of the proteins showed a decrease in the number of cancer cells in a dose-dependent manner, while the number of normal cells stayed relatively consistent. Tests using different combinations of SipA and RE-NLS proteins were able to show specifically SipA's cancer targeting activity. Conclusions/Discussion Thus, this study gives positive evidence that the SipA protein could potentially be a useful mediator for cancer specific drug delivery in the future.