These authors contributed equally to the manuscript.
The dietary terpene lupeol targets colorectal cancer cells with constitutively active Wnt/β-catenin signaling
Article first published online: 9 JUL 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 11, pages 1950–1958, November 2013
How to Cite
Tarapore, R. S., Siddiqui, I. A., Adhami, V. M., Spiegelman, V. S. and Mukhtar, H. (2013), The dietary terpene lupeol targets colorectal cancer cells with constitutively active Wnt/β-catenin signaling. Mol. Nutr. Food Res., 57: 1950–1958. doi: 10.1002/mnfr.201300155
- Issue published online: 28 OCT 2013
- Article first published online: 9 JUL 2013
- Manuscript Accepted: 27 APR 2013
- Manuscript Revised: 25 APR 2013
- Manuscript Received: 27 FEB 2013
- National Institutes of Health. Grant Numbers: R01-120451;, R01-CA121851
- postdoctoral fellowship by U.S.. Grant Number: T32AR055893
- Mentored Research Scholar. Grant Number: MRSG-11-019-01-CNE
- American Cancer Society
- Colorectal cancer;
- Dietary triterpene;
- β catenin pathway
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.
In summary, our data strongly advocate the efficacy of lupeol against CRC cells that exhibit constitutively active Wnt/β-catenin signaling.