Health Science Reviews

By Athianda Bukula

Who would have thought that the microscopic world of bacteria could offer new hope in the fight against cancer? As cancer research continues to explore many approaches, one unexpected candidate has emerged from bacterial systems: the MazF-MazE toxin -antitoxin system. At the heart of this mechanism is MazF. A bacterial toxin that halts cell function by cleaving messenger RNA (mRNA), effectively shutting down protein synthesis and triggering cell death. Could this bacterial enzyme be key to future cancer therapy? 

MazF Escherichia coli is an endoribonuclease found in Escherichia coli that specifically cleaves mRNAs at ACA sequences. MazE serves as an antitoxin by blocking MaF’s endoribonuclease activity, thereby preventing cell death in bacteria. MaF when introduced into mammal cells, has been shown to trigger programmed cell death. 

The study done by Shimazu et al., (2014) demonstrated that sustained expression of wildtype MaF expression significantly reduce tumor size in nude mice and with MazF counteracts the MazF-induced tumor regression. They developed a tetracycline-inducible system to control MazF expression in human kidney cells (T-Rex 293), using plasmids to stably express either MazF alone or with its antitoxin MazE. The 293 (mazF/pcDNA3) cell line was injected into 8 nude mice to form tumors and tumor growth was monitored 45 days. MazF was induced with doxycycline to observe its effect on tumour size and also control tumor size without MazF induction was monitored. 

Findings 

In Figure 1a below, the control mice (without MazF induction) show steady tumor growth over 28 days as expected.  In Figure 1b, MazF was induced in 4 mice, leading to dramatic reduction and complete regression of tumors. However, as shown in Figure1c, tumours in another group of 4 initially decreased after MazF induction but regrew within two weeks, likely due to loss or inactivation of MazF. Figure 1d highlights the role of the Maze. When the MazE was co- expressed with MazF, the tumors did not regress, demonstrating that MazE effectively blocks MazF’s tumor-killing action. 

The study took a closer look at why tumors regrew in the mice shown in Figure 1c. Using RTPCR and DNA sequencing, researchers discovered mutations in the MazF, leading to a loss of function and allowing the tumors to regrow. 

In conclusion, the findings of this study clearly demonstrate that MazF has promising antitumor activity in vivo. It shows real potential as a novel anti-cancer agent by inducing tumor regression through targeted mRNA degradation. However, challenges remain, particularly regarding specificity, as MazF may also affect normal cells, and ethical concerns may arise with its application. Still, if these issues are carefully addressed, this humble bacterial toxin might one day become a powerful tool in cancer therapy. 

Reference 

Shimazu, T. et al. (2014) “Regression of Solid Tumors by Induction of MazF, a Bacterial mRNA Endoribonuclease,” Journal of Molecular Microbiology and Biotechnology, 24(4), pp. 228–233. 

Available at: https://doi.org/10.1159/000365509.