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The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer

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Abstract

Multiple cellular signaling pathways have been involved in the processes of cancer cell invasion and metastasis. Among many signaling pathways, Wnt and Hedgehog (Hh) signaling pathways are critically involved in embryonic development, in the biology of cancer stem cells (CSCs) and in the acquisition of epithelial to mesenchymal transition (EMT), and thus this article will remain focused on Wnt and Hh signaling. Since CSCs and EMT are also known to be responsible for cancer cell invasion and metastasis, the Wnt and Hedgehog signaling pathways are also intimately associated with cancer invasion and metastasis. Emerging evidence suggests the beneficial role of chemopreventive agents commonly known as nutraceutical in cancer. Among many such agents, soy isoflavones, curcumin, green tea polyphenols, 3,3′-diindolylmethane, resveratrol, lycopene, vitamin D, etc. have been found to prevent, reverse, or delay the carcinogenic process. Interestingly, these agents have also shown to prevent or delay the progression of cancer, which could in part be due to their ability to attack CSCs or EMT-type cells by attenuating the Wnt and Hedgehog signaling pathways. In this review, we summarize the current state of our knowledge on the role of Wnt and Hedgehog signaling pathways, and their targeted inactivation by chemopreventive agents (nutraceuticals) for the prevention of tumor progression and/or treatment of human malignancies.

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Acknowledgements

The authors’ work cited in this review article was funded by grants from the National Cancer Institute, NIH (5R01CA083695, 2R01CA108535, 5R01CA131151, 3R01CA131151-02S109, and 1R01CA132794 awarded to FHS), and a sub-contract award to FHS from the University of Texas MD Anderson Cancer Center through SPORE grant (5P20-CA101936, 3P20CA101936-05S109) on pancreatic cancer awarded to James Abbruzzese. We also thank Puschelberg and Guido foundations for their generous contribution to support our research.

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  1. Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 740 HWCRC, 4100 John R Street, Detroit, MI, 48201, USA

    Fazlul H. Sarkar, Yiwei Li, Zhiwei Wang & Dejuan Kong

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  1. Fazlul H. Sarkar
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  2. Yiwei Li
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Correspondence to Fazlul H. Sarkar.

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Sarkar, F.H., Li, Y., Wang, Z. et al. The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer. Cancer Metastasis Rev 29, 383–394 (2010). https://doi.org/10.1007/s10555-010-9233-4

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