Suicide gene therapy: ldrB genes from E.coli as a potential tool against cancer

Y Jimenez Martinez(1) J Asensio Lopez(1) J Peña Martin(1) G Jimenez Gonzalez(1) C Griñan Lison(1) J A Marchal Corrales(1) H Boulaiz Tassi(1)

1:Universidad de Granada

Cancer is one of the diseases with the highest mortality at present. Due to this it is necessary to develop new more effective therapies with fewer side effects. The use of suicide gene therapy can be a novel tool for this. Here, we evaluate the cytotoxic impact of ldrB toxin of Escherichia coli. For that purpose, colorectal, breast and cervix cancer cells were transfected under the control of TRE3G promoter inducible by doxycycline. Our results showed a decrease in cell proliferation in the HeLa, MCF7 and HCT116 cancer cell line. On the other hand, the mechanism of action of cell death is revealed through the development of a western blot protocol, showing the presence of proteins involved in pyroptosis in the transfected cells with respect to the control. Scanning electron microscopy shows that ldrB toxin generates a decrease in cell density and creates large pores in the membrane that can lead to cell death. The appearance of large-sized pyroptotic bodies is also observed, as well as the rupture of the membrane. Taken together, our results provide proof of the antitumor effect of this toxin in colorectal, breast and cervical cancer, and a sample of the potential of suicide gene therapy as an anticancer tool.