Diallyl disulfide (DADS) boosts TRAIL-Mediated apoptosis in colorectal cancer cells by inhibiting Bcl-2

Hong Jun Kim1, Sanghee Kang2, Dae Yeoung Kim3

  • 1Department of Oncology, Korea University Guro Hospital, 148 Gruodong-gil, Guro-gu, Seoul, 08308, Republic of Korea.

Insights

Diallyl disulfide (DADS) enhances TRAIL-induced apoptosis in colorectal cancer (CRC) by down-regulating Bcl-2. This combination therapy shows promise for overcoming TRAIL resistance in CRC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Colorectal cancer (CRC) treatment progress has lagged behind other cancers.
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis but faces resistance.
  • Novel strategies are needed to overcome TRAIL resistance in CRC.

Purpose of the Study:

  • To investigate the efficacy of diallyl disulfide (DADS) in overcoming TRAIL resistance in CRC.
  • To elucidate the molecular mechanisms underlying the synergistic effects of DADS and TRAIL.
  • To evaluate the in vivo therapeutic potential of DADS combined with TRAIL.

Main Methods:

  • Treatment of CRC cell lines with non-cytotoxic doses of DADS and TRAIL.
  • In vivo studies using nude mice to assess synergistic effects.
  • Analysis of Bcl-2 protein expression in response to DADS and TRAIL treatment.

Main Results:

  • Non-cytotoxic DADS doses significantly increased TRAIL-associated cell death in CRC cell lines.
  • Synergistic anti-cancer effects of DADS and TRAIL were confirmed in vivo.
  • Down-regulation of the anti-apoptotic protein Bcl-2 was identified as a key mechanism.
  • Overexpression of Bcl-2 attenuated the synergistic effect of DADS and TRAIL.

Conclusions:

  • DADS sensitizes CRC cells to TRAIL-induced apoptosis.
  • The combination of DADS and TRAIL offers a potential therapeutic strategy for CRC.
  • Inhibition of Bcl-2 by DADS is crucial for enhancing TRAIL-mediated anti-cancer effects.

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