Programmed cell death (PCD), an active process that leads to cell suicide, is a critical mechanism in every organism. MazF, a bacterial ribonuclease protein, can trigger PCD in bacterial cells and also induce Bak-dependent apoptosis in mammalian cells. This bacterial ribonuclease cleaves mRNAs at ACA sequences leading to inhibition of protein synthesis in cells. Hence, we hypothesized that the overexpression of MazF proteins in cancer cells could result in the induction of apoptosis. In the present study, the ACA-less mazF gene was inserted downstream of the Internal Ribosome Entry Site (IRES) and under the control of T7 promoter. The plasmid was electroporated into Listeria monocytogenes harboring pCSA1 that encodes T7 RNA polymerase under the control of the listeria actA promoter. Subsequently, the bacteria were functionalized with Trastuzumab (Herceptin®) to deliver the mazF mRNA into HER2/neu breast cancer cells. The results showed that MazF protein has an ability to induce apoptosis in HER2/neu breast cancer cells. This finding is the first report of the application and delivery of MazF as an anti-cancer agent for the induction of apoptosis in HER2/neu breast cancer cell line. This research suggests cancer therapy that targets only cancer cells but not healthy cells and offers more advantages, e.g., inexpensiveness, target tissue specificity, easy and safe delivery, in comparison to other gene therapy vectors or direct protein administration.
Citation Format: Maryam Saffarian, Jeremy Tzeng. Exclusive delivery of mazF in cancer cells by Listeria monocytogenes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4314. doi:10.1158/1538-7445.AM2017-4314