13106 Background: The use of live or attenuated pathogenic bacteria in the treatment of cancer dates back to the late nineteen hundreds when William B. Coley first reported that inducing Streptococcal infection resulted in tumor regression. However, the hazards of using live bacteria are obvious. Similarly, the results of using attenuated bacteria have been spotty and enthusiasm for it has waxed and waned. Recently, we have shown that redox protein azurin (14 kDa) secreted by an opportunistic pathogen, Pseudomonas aeruginosa, is not only cytotoxic to cancer cells in vitro but also produces tumor regression in athymic mice without producing any toxicity (PNAS, 99, 14098–14103, 2002; Science’s STKE, 158, tw416, 2002). Methods: In this study, we show the effect of 1mg/kg of azurin injected i.p. starting 72 hours after inoculation of 5x107 MCF-7 breast cancer cells in estradiol pretreated nude mice for 28 days (n = 20, control = 10, azurin-treated = 10). Results: Univariate analysis of the data showed the difference in tumor growth rates between control animals and azurin-treated animals was significant. For instance, 22 days after the start of treatment, the mean tumor volume in azurin-treated animals was only 22% of the mean tumor volume in the control mice (i.e., 0.0267 cm3 + 0.124 cm3 respectively, P = 0.0179 Kruskal-Wallis test). At the end of the experiment on the 29th day there was a reduction in the tumor volume by 85% in the treated group. We used a multivariate model, where the tumor growth over time was taken to be exponential with coefficients that were subject specific mixed effect (For control, tumor volumes = exp (−4.23 + 0.06 time) while for the treated group it was tumor volume = exp (−4.23 + 0.03 time)). The difference is statistically significant (P = 0.0456). Taken together, this in vivo data shows azurin exerts an inhibitory effect in the growth and progression of MCF-7 tumor xenotransplants. During the 28 days of treatment, treated animals did not show any sign of toxicity. Conclusions: Bacterial redox protein azurin can be explored as a novel therapeutic agent for treatment of breast cancer. Recently, we have prepared a truncated version of azurin which has 28 amino acids. It appers that this chemically synthesized peptide (2.8 kDa) has similar properties as azurin. No significant financial relationships to disclose.
Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression
