Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells.

Polyphenols have shown promising bioactivity in experimental in vitro and in vivo models for cancer chemoprevention. However, consumed orally, they are often transformed by gut microbes into new active principles with so far incompletely deciphered molecular mechanisms. Here, enterolacton, S-equol and urolithin A as representatives of metabolites of lignans, isoflavones and ellagitannins, respectively, were examined for their impact on HCT116 colon cancer cell growth, cooperativity with oxaliplatin and p53 dependency in vitro. Whereas enterolacton and S-equol (≤60 µM) did not elicit growth inhibition or positive cooperativity with oxaliplatin, urolithin A showed an IC50 value of 19 µM (72 h) and synergism with oxaliplatin. Urolithin A induced p53 stabilization and p53 target gene expression, and absence of p53 significantly dampened the antiproliferative effect of urolithin A (IC50(p53-/-) = 38 µM). P53 was dispensable for the G2/M arrest in HCT116 cells but required for induction of a senescence-like phenotype upon long-term exposure and for the observed synergism with oxaliplatin. Moreover, extracellular flux analyses and knockdown approaches uncovered a reduced glycolytic potential via the p53/TIGAR axis which was linked to the higher susceptibility of wildtype cells to urolithin A. Overall, the p53 status turned out to be an important determinant for the potential benefit of dietary ellagitannins in cancer chemoprevention or use in adjuvant therapy.

Effectiveness of aggression replacement training in reducing criminal recidivism among convicted adult offenders.

BACKGROUND: Aggression replacement training (ART) is a widely used cognitive behavioural intervention for reducing aggression-related recidivism among criminal offenders. Its effectiveness in reducing offending, however, remains uncertain. AIM: To examine the effect of ART on adult offenders' criminal recidivism rates. METHOD: We compared 1,124 convicted adult offenders who began ART in the Swedish Prison and Probation Services 2003-2009 with 3,372 offenders in the system at the same time who did not participate in ART. Linkage with nationwide, longitudinal registries allowed extensive propensity score-matched controlling for baseline differences (e.g. sociodemographics, criminal history, psychiatric morbidity, and substance misuse) between groups. RESULTS: Intent-to-treat analyses suggested similar 1-year general reconviction rates (according to the National Crime Register) between the two groups (ART participants 50% [n = 465]: comparison participants 51% [n = 1,492]; hazard ratio [HR] = 0.97, 95% CI [0.88, 1.07]) and similar one-year violent recidivism (ART participants 19% [n = 174]: comparison participants 18% [n = 547]; HR = 1.02, 95% CI [0.89, 1.17]). For ART completers, findings suggested a marginal decrease in reconvictions for any recidivism, but not for violent recidivism specifically. Sensitivity analyses yielded similar results. CONCLUSIONS AND IMPLICATIONS: Our findings add to the emerging literature suggesting no effect of ART on reoffending among adult offenders. Originally designed for adolescents, it may be that the programme should include components for more adult-specific needs. Further, although group differences in reoffending did not emerge, research with a wider range of outcomes may be worthwhile before abandoning this approach with offenders.