The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth

Christopher M. Cabello, Warner B. Bair, Sarah D. Lamore, Stephanie Ley, Alexandra S. Bause, Sara Azimian, Georg T Wondrak

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Redox dysregulation in cancer cells represents a chemical vulnerability that can be targeted by pro-oxidant redox intervention. Dietary constituents that contain an electrophilic Michael acceptor pharmacophore may therefore display promising chemopreventive and chemotherapeutic anti-cancer activity. Here, we demonstrate that the cinnamon-derived dietary Michael acceptor trans-cinnamic aldehyde (CA) impairs melanoma cell proliferation and tumor growth. Feasibility of therapeutic intervention using high doses of CA (120 mg/kg, po, daily, 10 days) was demonstrated in a human A375 melanoma SCID mouse xenograft model. Low-micromolar concentrations (IC50 < 10 μM) of CA, but not closely related CA derivatives devoid of Michael acceptor activity, suppressed proliferation of human metastatic melanoma cell lines (A375, G361, LOX) with G1 cell-cycle arrest, elevated intracellular ROS, and impaired invasiveness. Expression array analysis revealed that CA induced an oxidative stress response in A375 cells, up-regulating heme oxygenase 1, sulfiredoxin 1 homolog, thioredoxin reductase 1, and other genes, including the cell-cycle regulator and stress-responsive tumor suppressor gene cyclin-dependent kinase inhibitor 1A, a key mediator of G1-phase arrest. CA, but not Michael-inactive derivatives, inhibited NF-κB transcriptional activity and TNFα-induced IL-8 production in A375 cells. These findings support a previously unrecognized role of CA as a dietary Michael acceptor with potential anti-cancer activity.

Original languageEnglish (US)
Pages (from-to)220-231
Number of pages12
JournalFree Radical Biology and Medicine
Volume46
Issue number2
DOIs
StatePublished - Jan 15 2009

Fingerprint

Cinnamomum zeylanicum
Cell proliferation
Tumors
Melanoma
Cell Proliferation
Growth
Cells
Neoplasms
Oxidation-Reduction
Thioredoxin Reductase 1
Genes
Derivatives
G1 Phase Cell Cycle Checkpoints
cdc Genes
Heme Oxygenase-1
Oxidative stress
SCID Mice
Cyclin-Dependent Kinases
G1 Phase
cinnamic aldehyde

Keywords

  • Cinnamic aldehyde
  • Free radicals
  • Melanoma
  • Michael acceptor
  • NF-κB
  • Oxidative stress
  • p21 (CDKN1A)
  • Xenograft

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth. / Cabello, Christopher M.; Bair, Warner B.; Lamore, Sarah D.; Ley, Stephanie; Bause, Alexandra S.; Azimian, Sara; Wondrak, Georg T.

In: Free Radical Biology and Medicine, Vol. 46, No. 2, 15.01.2009, p. 220-231.

Research output: Contribution to journalArticle

Cabello, Christopher M. ; Bair, Warner B. ; Lamore, Sarah D. ; Ley, Stephanie ; Bause, Alexandra S. ; Azimian, Sara ; Wondrak, Georg T. / The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth. In: Free Radical Biology and Medicine. 2009 ; Vol. 46, No. 2. pp. 220-231.
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