Original ContributionThe cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth
Section snippets
Chemicals
All chemicals were from Sigma Chemical Co. (St. Louis, MO, USA).
Human melanoma SCID mouse xenograft model
A375 human melanoma cells were grown in HyQ RPMI 1640 medium (HyClone) supplemented with 10% fetal bovine serum (Omega Scientific) and maintained in 5% CO2–95% air humidified atmosphere at 37 °C. Subconfluent cells were harvested by using 0.25% trypsin–EDTA (HyClone). Cells (> 90% viability) were resuspended at the concentration of 10 × 106 cells /100 μl of sterile saline. A SCID mouse colony was developed at the University of Arizona
Oral administration of cinnamic aldehyde impairs growth of A375 human melanoma xenografts in SCID mice
Based on its known safety profile as a human dietary factor, its documented low acute toxicity in mice (oral LD50 > 2 g/kg in mice [36]), and promising cell-based chemopreventive properties [32], we tested the thiol-reactive Michael acceptor CA as a potential inhibitor of tumor growth in a human melanoma SCID mouse xenograft model (Fig. 1). Daily oral CA treatment (120 mg/kg/day in 0.5% methylcellulose/PBS) of human A375 melanoma xenograft-bearing SCID mice induced a moderate suppression of
Discussion
The preferential sensitivity of melanoma cells to small-molecule pro-oxidant intervention [12], [13], [14], [15], [16], [18] and the documented anti-melanoma activity of electrophilic agents that share a Michael acceptor pharmacophore, including curcumin [40], [41], dimethylfumarate [15], omentosin, and inuviscolide [42], led us to evaluate the anti-melanoma activity of CA in vitro and in vivo. CA, a key flavor compound contained in the essential oil of cinnamon, contains an electrophilic
Acknowledgments
This work was supported in part by grants from the National Institutes of Health (R01CA122484, ES007091, Arizona Cancer Center Support Grant CA023074) and from the Arizona Biomedical Research Commission (ABRC 0721). Animal experimentation was performed at the AZCC Experimental Mouse Shared Service and tumor histology was performed at the Tissue Acquisition and Cellular/Molecular Analysis Shared Service.
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2021, Colloids and Surfaces A: Physicochemical and Engineering AspectsCitation Excerpt :Hyun et al. found that a unique plant polyphenol, which contained a CA skeleton structure, caused an incomplete cell cycle by blocking the G2/M phase, thereby inducing human ovarian cancer cell death [9]. Azimian et al. indicated that CA induces apoptotic cell death and inhibits tumor growth, by inhibiting the activity of NF-κB and the production of interleukin-8 (IL-8) [10–12]. Cabello et al. found that CA at low molar concentration inhibited the proliferation of human metastatic melanoma A375 cell line with increased intracellular ROS [13].
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