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

105 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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