3,3′-Diindolylmethane induces apoptosis and autophagy in fission yeast

Abstract

3,3′-Diindolylmethane (DIM) is a compound derived from the digestion of indole-3-carbinol, found in the broccoli family. It induces apoptosis and autophagy in some types of human cancer. DIM extends lifespan in the fission yeast Schizosaccharomyces pombe. The mechanisms by which DIM induces apoptosis and autophagy in humans and expands lifespan in fission yeasts are not fully understood. Here, we show that DIM induces apoptosis and autophagy in log-phase cells, which is dose-dependent in fission yeast. A high concentration of DIM disrupted the nuclear envelope (NE) structure and induced chromosome condensation at an early time point. In contrast, a low concentration of DIM induced autophagy but did not disrupt NE structure. The mutant defective in autophagy was more sensitive to a low concentration of DIM, demonstrating that the autophagic pathway contributes to the survival of cells against DIM. Moreover, our results showed that the lem2 mutant is more sensitive to DIM. NE in the lem2 mutant was disrupted even at the low concentration of DIM. Our results demonstrate that the autophagic pathway and NE integrity are important to maintain viability in the presence of a low concentration of DIM. The mechanism of apoptosis and autophagy induction by DIM might be conserved in fission yeast and humans. Further studies will contribute to the understanding of the mechanism of apoptosis and autophagy by DIM in fission yeast and humans.