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Published on: October 5, 2012
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.
Abstract:
Ever since several targeted agents were introduced a decade ago, progress in new therapeutic strategies for colorectal cancer (CRC) has been much slower than that for other cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is widely known to induce cellular apoptosis in numerous cancer cell types. However, many cancer cells are resistant to the effects of TRAIL, and thus, approaches are needed to overcome TRAIL resistance. We demonstrated that non-cytotoxic doses of diallyl disulfide (DADS) increased TRAIL-associated cell death in CRC cell lines. Additionally, synergistic effects between DADS and TRAIL were validated in vivo in nude mice. One process involved in these effects includes down-regulation of the anti-apoptotic protein Bcl-2, and the synergistic effect of DADS with TRAIL was attenuated in Bcl-2-over-expressing cells. Taken together, the results of this study give new insights into the role of DADS in TRAIL-related repression of CRC progression by inhibition of Bcl-2.
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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