Differential roles of 2, 6, and 8 carbon ceramides on the modulation of gap junctional communication and apoptosis during carcinogenesis

Brad L. Upham*, Tyler R. Koski, Alisa M. Rummel, Melinda R. Wilson, Anelia Horvath, James E. Trosko

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The inhibition of apoptosis and gap junctional intercellular communication (GJIC) has been implicated in tumor promotion. Ionizing radiation and oxidative toxicants activate sphingomyelinases resulting in the release of ceramides that control cell proliferation and apoptosis. A rat liver epithelial cell line treated with ceramides containing a 6 (C6) or 8 (C8) carbon acyl-group were potent inhibitors of GJIC and apoptosis, whereas a C2-ceramide was only a weak inhibitor of GJIC and strong inducer of apoptosis. Apoptosis induced by either serum deprivation or C2-ceramide was inhibited by the GJIC inhibitory C8-ceramide. In conclusion, these results suggest that a chronic release of ceramides with acyl groups larger than C6 might act as tumor promoters.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalCancer Letters
Volume191
Issue number1
DOIs
StatePublished - Feb 28 2003

Keywords

  • Apoptosis
  • Ceramide
  • Gap junctional intercellular communication
  • Signal transduction
  • Tumor promotion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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