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Mol Nutr Food Res. 2013 Nov;57(11):1950-8. doi: 10.1002/mnfr.201300155. Epub 2013 Jul 9.

The dietary terpene lupeol targets colorectal cancer cells with constitutively active Wnt/β-catenin signaling.

Author information

1
Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA; Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.

Abstract

SCOPE:

Aberrant activation of the Wingless-type mouse mammary tumor virus integration site family (Wnt)/β-catenin signaling pathway is the most common modification, and often considered, a hallmark of colorectal cancer (CRC). Typically in this pathway the β-catenin translocates from the cytoplasm to the nucleus, where it functions as a transcription regulator of several genes that support tumor formation and progression. Thus, any agent that could attenuate the translocation of β-catenin could be extremely valuable against CRC, especially the tumors that exhibit constitutively active Wnt/β-catenin signaling.

METHODS AND RESULTS:

Using human CRC cells that exhibit differential expression of Wnt/β-catenin signaling, we demonstrate that treatment of CRC cells with dietary triterpene lupeol results in a dose-dependent (i) decrease in cell viability, (ii) induction of apoptosis, (iii) decrease in colonogenic potential, (iv) decrease in β-catenin transcriptional activity, and (v) decrease in the expression of Wnt target genes. Most importantly lupeol was observed to inhibit the translocation of β-catenin from the cytoplasm to the nucleus. Importantly, all these effects of lupeol were restricted to cells that harbor constitutively active Wnt/β-catenin signaling while negligible effects were observed in cells that lack constitutively active Wnt/β-catenin signaling. Further, we also demonstrate that inhibition of Wnt signaling in cells with constitutive active Wnt/β-catenin results in loss of lupeol efficacy while inducing Wnt signaling sensitizes the cells to inhibitory effects of lupeol.

CONCLUSION:

In summary, our data strongly advocate the efficacy of lupeol against CRC cells that exhibit constitutively active Wnt/β-catenin signaling.

KEYWORDS:

Chemoprevention; Colorectal cancer; Dietary triterpene; Lupeol; Wnt; β catenin pathway

PMID:
23836602
PMCID:
PMC3865779
DOI:
10.1002/mnfr.201300155
[Indexed for MEDLINE]
Free PMC Article

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