The proteasome inhibitor bortezomib (Velcade) sensitizes some human tumor cells to Apo2L/TRAIL-mediated apoptosis

Alan D. Brooks, Teresa Ramirez, Uhi Toh, Jennifer Onksen, Peter J. Elliott, William J Murphy, Thomas J. Sayers

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

On testing a panel of different human cancer cell lines, we observed that the proteasome inhibitor bortezomib could dramatically sensitize some lines to the apoptotic effects of Apo2L/TRAIL. Certain renal, colon, or breast tumor cell lines were dramatically sensitized, whereas other tumor lines from the same tissue of origin remained resistant. This sensitization did not correlate with either the p53 status of the individual tumor cell lines or their intrinsic sensitivity to Apo2L/TRAIL. Colon cancer cell lines lacking p53 or Bax were sensitized by bortezomib, suggesting that neither p53 nor Bax levels were crucial for sensitization. Although the molecular basis of bortezomib sensitization of tumor cells to Apo2L/TRAIL remains to be determined, this combination can have an enhanced apoptotic effect over either agent alone for certain human cancer cells.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1059
DOIs
StatePublished - 2005
Externally publishedYes

Keywords

  • Apo2L/TRAIL
  • Apoptosis
  • Bortezomib
  • Velcade

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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