Abstract
ObjectiveDespite recent advances in treatment options, pancreatic cancer remains the most deadly major cancer. Targeting metabolism represents an emerging anti-cancer strategy.ResultsMetagenomic 16S analysis was employed to explore the effect of Dichloroacetate (DCA) on the composition of the fecal microbiota and metabolomic profile was assessed on in vivo pancreatic cancer mouse xenograft model. Pancreatic cancer xenograft mice displayed a shift of microbiota’ profile as compared to control mice without DCA treatment and a significant decrease of the purine bases inosine xanthine together with their metabolically-related compound hypoxanthine were observed in the DCA treated group as compared to the control group. Two aminoacids methionine and aspartic acid resulted decreased and increased respectively. DCA affects tumor environment and studies are needed in order to understand whether DCA supplementation could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.
Highlights
Pancreatic cancer (PC) is one of the most aggressive and highly lethal tumor ranked as the fourth leading cause of cancer-related deaths worldwide and it is expected to become the second leading cause of cancer death in the decade
We recently demonstrated that DCA-treated PANC-1 and BXPC-3 cells showed a marked decrease in cell proliferation and migration combined with an enhanced ROS production resulting in a mitigation of tumor growth in pancreatic cancer xenografted mice [8]
Being DCA an effective modulator of glucose metabolism, in this manuspcript we assessed the effect of DCA on microbiota and metabolomic profile on the above mentioned in vivo model of pancreatic cancer xenografted mice
Summary
Effect of DCA on microbiota profile of PC xenograft mice Beside the trend in retarding tumor growth without reaching statistical significance (Fig. 1a) as previously published [11], DCA treatment did not have significant effect on the fecal microbiota on the phylum level and the two main phyla were Firmicutes and Bacteroidetes with lower abundance of Proteobacteria and Verrucomicrobia (average abundances: 39, 38, 17 and 5%, and 58, 24, 17 and 1% in control and DCA mice, respectively). DCA treated mice can be characterized by dominance of Lachnospiraceae. Metabolomic profile in DCA treated xenograft mice Serum samples collected from both control and DCAtreated animals were collected to evaluate the metabolomic profile. A total of 38 out of 97 compounds were detected (Fig. 2). Among these compounds, a significant decrease of the purine bases inosine xanthine together with their metabolicallyrelated compound hypoxanthine were observed in the DCA treated group as compared to the control group. Two aminoacids methionine and aspartic acid resulted decreased and increased respectively
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