Ceramide accumulation precedes caspase-3 activation during apoptosis of A549 human lung adenocarcinoma cells

Tommer Ravid, Adili Tsaba, Peter Gee, Reuven Rasooly, Edward A. Medina, Tzipora Goldkorn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Ceramide, the basic structural unit of sphingolipids, controls the balance between cell growth and death by inducing apoptosis. We have previously shown that accumulation of ceramide, triggered by hydrogen peroxide (H2O2) or by short-chain ceramide analogs, induces apoptosis of lung epithelial cells. Here we elucidate the link between caspase-3 activation, at the execution phase, and ceramide accumulation, at the commitment phase of apoptosis in A549 human lung adenocarcinoma cells. The induction of ceramide accumulation by various triggers of ceramide generation, such as H2O2, C6-ceramide, or UDP-glucose-ceramide glucosyl-transferase inhibitor DL-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, triggered the activation of caspase-3. This ceramide elevation also induced the cleavage of the death substrate poly(ADP-ribose) polymerase and was followed by apoptotic cell death. Ceramide-mediated apoptosis was blocked by a general caspase inhibitor, Boc-D-fluoromethylketone, and by overexpression of the antiapoptotic protein Bcl-2. Notably, overexpression of Bcl-2 reduced the basal cellular levels of ceramide and prevented the induction of ceramide generation by C6-ceramide, which implies ceramide generation as a possible target for the antiapoptotic effects of Bcl-2.

Original languageAmerican English
Pages (from-to)L1082-L1092
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6 28-6
StatePublished - 1 Jun 2003
Externally publishedYes


  • Bcl-2 overexpression
  • Hydrogen peroxide
  • Sphingolipid signaling


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