Lactobacillus brevis T2102 suppresses the growth of colorectal cancer cells by activating SIRT1

• Establishment of a system for screening substances that activate the SIRT1 promoter.
• Identification of Lactobacillus brevis T2102 as a SIRT1-activating strain.
• Cancer growth suppression by T2102 through inactivating β-catenin.
• Transcriptional repression of hTERT gene by T2102.
• Cellular senescence induction by T2102.

SIRT1 is known to have critical functions in the maintenance of homeostasis and cell survival, and it confers anti-ageing effects on cells and tissues. To identify novel foods and food ingredients with potential anti-ageing functions, a novel system for screening substances that activate the SIRT1 promoter in human colorectal cancer cells was established. We screened several lactic acid bacteria (LAB) and identified Lactobacillus brevis T2102 as a SIRT1-activating strain of LAB. T2102 inactivated β-catenin through SIRT1-mediated deacetylation and consequently suppressed the growth of the human colorectal cancer cell line DLD-1. Furthermore, T2102-induced degradation of β-catenin repressed transcription of the human telomerase reverse transcriptase (hTERT) gene, one of the target genes of β-catenin, which led to the induction of cellular senescence and concomitant growth suppression of DLD-1. These results indicate that SIRT1-activating T2102 might be a promising candidate for developing novel functional foods with anti-cancer properties.