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

Rohinton S. Tarapore, Imtiaz A. Siddiqui, Vaqar M. Adhami, Vladimir S. Spiegelman, Hasan Mukhtar

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1950-1958
Number of pages9
JournalMolecular Nutrition and Food Research
Volume57
Issue number11
DOIs
StatePublished - Nov 2013

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

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