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

  • Ja Young Seol
  • , Kyung Ho Park
  • , Chang Il Hwang
  • , Woong Yang Park
  • , Chul Gyu Yoo
  • , Young Whan Kim
  • , Sung Koo Han
  • , Young Soo Shim
  • , Choon Taek Lee

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish
Pages (from-to)540-548
Number of pages9
JournalCancer Gene Therapy
Volume10
Issue number7
DOIs
StatePublished - 1 Jul 2003
Externally publishedYes

Keywords

  • Adenovirus
  • Apoptosis
  • Bystander effect
  • TRAIL
  • TRAIL resistance

Fingerprint

Dive into the research topics of 'Adenovirus-TRAIL can overcome TRAIL resistance and induce a bystander effect'. Together they form a unique fingerprint.

Cite this