Bacteria-directed
enzyme prodrug therapy (BDEPT), is an emerging alternative directed and
tumor-specific approach. The basis of this method is the conversion of a non-toxic
prodrug by a bacterial
enzyme to a toxic
drug within the tumor-microenvironment (TME). In the present study, the therapeutic efficacy of BDEPT was investigated based on the ability of Escherichia coli DH5α-lux/βG in activation of
glycyrrhizic acid (GL), a natural and non-toxic compound purified from licorice, to
glycyrrhetinic acid (GA) only in TME. To do so, the anti-bacterial effects of GL on bacteria and the cytotoxic effects of the produced GA on survival rate of CT26 mouse colon
carcinoma cells were evaluated. The IC50 values of the produced GA and
cisplatin were determined as 210 μM and 100 μM, respectively. Comparing these values to GL treatment (1305 μM) indicates that bacteria could have efficiently activated GL to GA to inhibit the growth of
tumor cells. Afterward, the anti-
cancer effects of bacteria used in combination with GL was investigated in a mouse model of colon
carcinoma. Results were indicative of targeted homing and even proliferation of luminescent bacteria in TME. Moreover, combined treatment greatly inhibited
tumor growth. Histopathological analysis of dissected tissues also demonstrated increased apoptosis rate in
tumor cells after combined treatment and interestingly, showed no obvious damage to the spleen and liver of treated mice. Accordingly, this BDEPT approach could be considered as an effective alternative
tumor-specific
therapy utilizing
prodrug-activating
enzymes expressing from
tumor-targeting bacteria to allow the development of new
tumor-specific
pharmacotherapy protocols.