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Adenovirus-TRAIL can overcome TRAIL resistance and induce a bystander effect

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Abstract

TRAIL is a cytokine with a unique ability to induce apoptosis selectively in many transformed cell lines. The instability of TRAIL and the resistance of some cancer cells to TRAIL present the main obstacles for clinical experimentation. We generated an adenovirus expressing full-length TRAIL and tested its efficacy in several cancer cell lines. Ad-TRAIL-infected cancer cells localized full-length TRAIL protein to the cytoplasm and released same-sized TRAIL in the media. Ad-TRAIL was found to induce apoptotic cell death in several cancer cell lines resistant to soluble TRAIL (A549, SKOV3, HT-29 and LNCap) and in TRAIL-sensitive cell lines. Ad-TRAIL, but not soluble TRAIL, induced apoptotic cell death in TRAIL-resistant cell lines, manifested by an increased sub-G1 proportion, caspase-3 activation and PARP cleavage. Ad-TRAIL also induced a media-transferable bystander effect, but only in soluble TRAIL-sensitive cell lines. In conclusion, two novel characteristics of ad-TRAIL were found during this study. First, that ad-TRAIL can induce apoptotic cell death in several cancer cell lines resistant to sTRAIL. Second, that ad-TRAIL induces a media-transferable bystander effect, which is expected to increase its therapeutic value by allowing TRAIL to overcome the locally acting nature and low transduction rate commonly encountered in clinical situation.

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Abbreviations

TRAIL:

Tumor necrosis factor related apoptosis inducing ligand

Ad-TRAIL:

Adenovirus expressing TRAIL

sTRAIL:

soluble TRAIL

CAR:

Coxsackie adenoviral receptor

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Acknowledgements

This study was supported by a grant (HMP-00-B-20800-0072) of the Good Health R&D Project, Ministry of Health & Welfare, Republic of Korea.

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Authors and Affiliations

  1. Department of Internal Medicine, Lung Institute of Medical Research Center, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, Korea

    Ja Young Seol, Kyung-Ho Park, Chul-Gyu Yoo, Young Whan Kim, Sung Koo Han, Young-Soo Shim & Choon-Taek Lee

  2. Department of Biochemistry and Molecular Biology and Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, Korea

    Chang-Il Hwang & Woong-Yang Park

  3. Clinical Research Institute, Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, Korea

    Chul-Gyu Yoo, Young Whan Kim, Sung Koo Han, Young-Soo Shim & Choon-Taek Lee

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  1. Ja Young Seol
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  2. Kyung-Ho Park
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Correspondence to Choon-Taek Lee.

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Seol, J., Park, KH., Hwang, CI. et al. Adenovirus-TRAIL can overcome TRAIL resistance and induce a bystander effect. Cancer Gene Ther 10, 540–548 (2003). https://doi.org/10.1038/sj.cgt.7700597

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  • DOI: https://doi.org/10.1038/sj.cgt.7700597

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