Promotion of TRAIL/Apo2L-induced apoptosis by low-dose interferon-β in human malignant melanoma cells

Akira Kazaana, Emiko Sano, Sodai Yoshimura, Kotaro Makita, Hiroyuki Hara, Atsuo Yoshino, Takuya Ueda

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Interferon β (IFN-β) is considered a signaling molecule with important therapeutic potential in cancer since IFN-β-induced gene transcription mediates antiproliferation and cell death induction. Whereas, TNF-related apoptosis inducing ligand/Apo2 ligand (TRAIL/Apo2L) has emerged as a promising anticancer agent because it induces apoptosis specifically in cancer cells. In this study, we elucidated that IFN-β augments TRAIL-induced apoptosis synergistically using five human malignant melanoma cells. All of these cells were induced apoptosis by TRAIL. Whereas, the response against IFN-β was different in amelanotic cells (A375 and CRL1579) and melanotic cells (G361, SK-MEL-28, and MeWo). The responsibility of amelanotic cells against IFN-β was higher than those of melanotic cells. The synergism of IFN-β and TRAIL were correlated with the responsibilities of the cells against IFN-β. The synergistic interaction was confirmed by a combination index based on the Chou-Talalay method. The upregulation of apoptosis in amelanotic cells was caused by very low doses of IFN-β (over 0.1 IU/ml). Both of p53-mediated intrinsic pathway and Fas-related extrinsic pathway were activated by IFN-β alone and combination with TRAIL. Further, TRAIL death receptors (DR4 and DR5) were upregulated by a low-dose IFN-β (over 0.1 IU/ml) and the expression was more promoted by the combination with TRAIL. It was clarified that the upregulation of DR5 is associated with the declination of viability.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - 2019 Jan 1
Externally publishedYes

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Keywords

  • apoptosis
  • DR4 and DR5
  • IFN-β
  • synergy of IFN-β and TRAIL
  • TRAIL/Apo2L

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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