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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

Authors: Cabello, Christopher M; Bair 3rd, Warner B; Lamore, Sarah D; Ley, Stephanie; Bause, Alexandra S; Azimian, Sara; Wondrak, Georg T

Published In Free Radic Biol Med, (2009 Jan 15)

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 (IC(50)< 10 microM) 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-kappaB transcriptional activity and TNFalpha-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.

PubMed ID: 19000754 Exiting the NIEHS site

MeSH Terms: Acrolein/analogs & derivatives*; Acrolein/pharmacology; Animals; Cell Line, Tumor; Cell Proliferation/drug effects*; Cinnamomum zeylanicum; Cyclin-Dependent Kinase Inhibitor p21/genetics; Cyclin-Dependent Kinase Inhibitor p21/metabolism; G1 Phase/drug effects; Gene Expression Profiling; Heme Oxygenase-1/genetics; Heme Oxygenase-1/metabolism; Humans; Interleukin-8/metabolism; Melanoma/drug therapy*; Melanoma/enzymology; Melanoma/pathology; Mice; Mice, SCID; Microarray Analysis; NF-kappa B/antagonists & inhibitors; Neoplasm Invasiveness/prevention & control; Neoplasm Transplantation; Oxidative Stress/drug effects; Oxidoreductases Acting on Sulfur Group Donors/genetics; Oxidoreductases Acting on Sulfur Group Donors/metabolism; Plant Growth Regulators/pharmacology*; Signal Transduction/drug effects; Thioredoxin Reductase 1/genetics; Thioredoxin Reductase 1/metabolism; Tumor Necrosis Factor-alpha/genetics; Tumor Necrosis Factor-alpha/metabolism

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