3,3'-Diindolylmethane induces apoptosis and autophagy in fission yeast.

Parvaneh Emami,Reiko Sugiura,Masaru Ueno

doi:10.1371/journal.pone.0255758

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.

Highlights

Apoptosis is a process that results in the death of damaged and unrepairable cells to maintain health in multicellular organisms [1]
To construct the ire1Δ::Kanr strain, we amplified the genomic DNA by polymerase chain reaction (PCR) using genomic DNA obtained from yPK002 as a template, a gift from Dr Walter [46], and the primers 5’-TGGATGACTATACCCAAAGC-3’ and 5’-ATCCAACGATCCCACAAGCG-3’
Our results show that DIM induces nuclear condensation and nuclear envelope (NE) disruption in log-phase cells, but not in stationary-phase cells within 10 minutes, which is much faster than nuclear fragmentation

Summary

Introduction

Apoptosis is a process that results in the death of damaged and unrepairable cells to maintain health in multicellular organisms [1]. It is a promising target for cancer therapy as it induces death in cancer cells [2]. Autophagy induction can suppress the growth of cancer cells [6,7,8,9]; it has several potential benefits to human health, including longevity and cancer therapy. Recent studies reported the anti-cancer effects of DIM through the induction of apoptotic cell death in breast cancer [11, 12], hepatoma [13, 14], prostate cancer [15, 16], or colon cancer [17,18,19]. DIM rapidly accumulates in the nuclear membranes (NM) of human breast

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Results

Conclusion