Abstract

The tannase-producing Gram-positive bacterial species Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathogen of the human gut and strongly associated with colorectal cancer (CRC). A unique feature of Sgg is its ability to degrade tannic acids (TA). TA constitute an important part of the human diet with known anti-tumorigenic properties. Here, we examined whether Sgg is able to protect tumor cells from the toxic effect of TA and thus drive tumorigenesis indirectly. Human CRC cell lines (n = 8) were treated with increasing concentrations of TA. We confirmed the cytotoxic activity of TA in a dose-dependent manner. In virtually all cell lines, viability decreased significantly (>60% inhibition). Moreover, pyrogallol, the degradation product of TA, had no effect on the tested cell lines. This suggests a specific effect of TA. Cytotoxicity was due to necrosis and induction of senescence in residual cells. Finally, when TA was degraded by Sgg, the cytotoxic effect could be abolished. Tumor cells even responded with boosted cell proliferation, highlighting the impact of Sgg on CRC progression. We here provide another piece of evidence for the active interplay between Sgg and cancer preventive components. These data will help to move forward in designing concepts for therapeutic and eventually also prophylactic approaches to combat gastrointestinal malignancies.

Highlights

  • The tannase-producing Gram-positive bacterial species Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathogen of the human gut and strongly associated with colorectal cancer (CRC)

  • The original division of the Streptococcus bovis/Streptococcus equinus complex (SBSEC) into S. bovis and S. equinus has further changed over the past years, reaching the current splitting into seven mainspecies, Streptococcus infantarius subsp. infantarius (Sii), Streptococcus lutetiensis, Streptococcus gallolyticus subsp. pasteurianus (Sgp), Streptococcus gallolyticus subsp. macedonicus (Sgm), Streptococcus gallolyticus subsp. gallolyticus (Sgg), Streptococcus alactolyticus and S. equinus[1,2,3]

  • Cells were maintained in full medium: DMEM/HamsF12 supplemented with 10% fetal calf serum (FCS), glutamine (2 mmol/L) and antibiotics

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Summary

Introduction

The tannase-producing Gram-positive bacterial species Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathogen of the human gut and strongly associated with colorectal cancer (CRC). Pyrogallol, the degradation product of TA, had no effect on the tested cell lines. Tumor cells even responded with boosted cell proliferation, highlighting the impact of Sgg on CRC progression We here provide another piece of evidence for the active interplay between Sgg and cancer preventive components. PG, the degradation product of TA, had no cytotoxic effect on the tested cell lines. When TA was degraded by Sgg, the toxic effect on the tumor cells could be abolished. This supports the assumption that colonization of the tumor by Sgg protects the tumor cells against otherwise toxic plant components that will be consumed by a normal human diet

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