TRAIL mediates apoptosis in cancerous but not normal primary cultured cells of the human reproductive tract

Anil Sadarangani, Sumie Kato, Natalia Espinoza, Soledad Lange, Carmen Llados, Marisol Espinosa, Manuel Villalón, Stanley Lipkowitz, Mauricio Cuello, Gareth I. Owen

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Cancer of the reproductive tract encompasses malignancies of the uterine corpus, cervix, ovary, Fallopian tube, among others and accounts for 15% of female cancer mortalities. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates apoptosis by binding to death receptors and offers a promising cancer treatment. The goal of this study was to investigate and characterize the effect of TRAIL in endometrial cancer cell lines and normal (non-cancerous) epithelial cells of endometrial origin. We also examined the effect of TRAIL in other primary cultured cancers and normal cells of the human female reproductive tract and evaluated if TRAIL mediated apoptosis correlated with death receptors and decoy receptors 1 and 2. Herein, we demonstrate that TRAIL at concentrations which kill cancerous cells, does not mediate apoptosis or alter cell viability in normal human endometrium, ovary, cervix or Fallopian tube. The partial inhibition by a caspase 9 inhibitor and the total inhibition by a caspase 8 inhibitor demonstrates the dependency on the extrinsic apoptotic pathway. The selective mortality does not correlate with the presence of death or decoy receptors. These results suggest that TRAIL may be an effective treatment for endometrial cancer and other female reproductive cancers, with minimal secondary effects on healthy tissue.

Original languageEnglish
Pages (from-to)73-85
Number of pages13
JournalApoptosis : an international journal on programmed cell death
Volume12
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a grant from the Wellcome Trust GR071469 (GIO) and the Chilean national science grants FONDECYT 1060495 (GIO) and 1020675 (MC).

Keywords

  • Cervix
  • Endometrium
  • Fallopian
  • Ovarian cancer

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