Cinnamaldehyde-induced apoptosis in human PLC/PRF/5 cells through activation of the proapoptotic Bcl-2 family proteins and MAPK pathway.

Cinnamaldehyde (Cin) has been shown to be effective in inducing apoptotic cell death in a number of human cancer cells. However, the intracellular death signaling mechanisms by which Cin inhibits tumor cell growth are poorly understood. In this study, we investigated the effect of mitogen-activated protein kinases (MAPKs) inhibitors [namely SP600125 (a specific JNK inhibitor), SB203580 (a specific p38 inhibitor) and PD98059 (a specific ERK inhibitor)] on the stress-responsive MAPK pathway induced by Cin in PLC/PRF/5 cells. Trypan blue staining assay indicated that Cin was cytotoxic to PLC/PRF/5 cells. Cin caused cell cycle perturbation (S-phase arrest) and triggered apoptosis as revealed by the externalization of annexin V-targeted phosphatidylserine and accumulation of sub-G1 peak. It down-regulated the Bcl-2 and Mcl-1 expression, and up-regulated Bax protein in a time-response manner. Treatment with 1 microM Cin resulted in an activation of caspase-8 and cleavage of Bid to its truncated form in a time-dependent pattern. JNK, ERK and p38 kinases in cells were activated and phosphorylated after Cin treatment. Pre-incubation with SP600125 and SB203580 markedly suppressed the effect of Cin-induced apoptosis, but not PD98059. Both SP600125 and SB203580 significantly prevented the phosphorylation of JNK and p38 proteins, but not ERK. These results conclude that Cin triggers apoptosis in PLC/PRF/5 cells could be through the activation of pro-apoptotic Bcl-2 family (Bax and Bid) proteins and MAPK signaling pathway.
AuthorsShu-Jing Wu, Lean-Teik Ng, Chun-Ching Lin
JournalLife sciences (Life Sci) Vol. 77 Issue 8 Pg. 938-51 (Jul 8 2005) ISSN: 0024-3205 [Print] England
PMID15964311 (Publication Type: Journal Article)
Chemical References
  • Annexin A5
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Acrolein
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • CASP8 protein, human
  • Caspase 8
  • Caspases
  • cinnamic aldehyde
  • Acrolein (analogs & derivatives, pharmacology)
  • Annexin A5 (metabolism)
  • Apoptosis (drug effects)
  • Carcinoma, Hepatocellular (metabolism, pathology)
  • Caspase 8
  • Caspases (metabolism)
  • Cell Proliferation (drug effects)
  • Enzyme Activation (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • G1 Phase (drug effects)
  • Humans
  • JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • MAP Kinase Signaling System (physiology)
  • Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
  • Phosphorylation (drug effects)
  • Proto-Oncogene Proteins c-bcl-2 (metabolism)
  • p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)

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