Abstract
The hedgehog (Hh) signaling pathway is an important therapeutic target in cancer; involvement of the Hh pathway has been shown in a variety of cancers including basal cell carcinoma, medulloblastoma, leukemia, and gastrointestinal, breast, prostate, lung, and pancreatic cancers [1-10]. Currently, several Hh pathway inhibitory drugs are in clinical development, and the FDA recently approved Erivedge (vismodegib) from Curis/Genentech [11-15]. These new drugs are effective in many, but not all patients [16]. In fact there are documented reports of tumors developing mutations that confer resistance to the drugs [14, 17-19]. This highlights the importance of finding second generation drugs that can be used on cancers that develop resistance to the first generation Hh inhibitors. Botanicals may serve as the backbone for such research. The gold-standard pathway inhibitor, cyclopamine, is itself a naturally occurring alkaloid found in Veratrum californicum [20]. In this review we will summarize the available literature on botanical compounds in Hh-related studies. In particular we will look at curcumin, genistein, EGCG, resveratrol, quercetin, baicalen, and apigenin along with novel compounds isolated from Southeast Asian plants, such as the potent sub-micromolar gitoxigenin derivatives. Due to the nature of the pathway, most of the research published has focused on functional Gli-transcriptional assays, which we will describe and summarize.
Keywords: Botanicals, cancer, dietary chemoprevention, gli, hedgehog signaling, nutraceuticals.
Current Cancer Drug Targets
Title:Inhibition of Hedgehog/Gli Signaling by Botanicals: A Review of Compounds with Potential Hedgehog Pathway Inhibitory Activities
Volume: 13 Issue: 5
Author(s): Sara K. Drenkhahn, Glenn A. Jackson, Anna Slusarz, Nicholas J.E. Starkey and Dennis B. Lubahn
Affiliation:
Keywords: Botanicals, cancer, dietary chemoprevention, gli, hedgehog signaling, nutraceuticals.
Abstract: The hedgehog (Hh) signaling pathway is an important therapeutic target in cancer; involvement of the Hh pathway has been shown in a variety of cancers including basal cell carcinoma, medulloblastoma, leukemia, and gastrointestinal, breast, prostate, lung, and pancreatic cancers [1-10]. Currently, several Hh pathway inhibitory drugs are in clinical development, and the FDA recently approved Erivedge (vismodegib) from Curis/Genentech [11-15]. These new drugs are effective in many, but not all patients [16]. In fact there are documented reports of tumors developing mutations that confer resistance to the drugs [14, 17-19]. This highlights the importance of finding second generation drugs that can be used on cancers that develop resistance to the first generation Hh inhibitors. Botanicals may serve as the backbone for such research. The gold-standard pathway inhibitor, cyclopamine, is itself a naturally occurring alkaloid found in Veratrum californicum [20]. In this review we will summarize the available literature on botanical compounds in Hh-related studies. In particular we will look at curcumin, genistein, EGCG, resveratrol, quercetin, baicalen, and apigenin along with novel compounds isolated from Southeast Asian plants, such as the potent sub-micromolar gitoxigenin derivatives. Due to the nature of the pathway, most of the research published has focused on functional Gli-transcriptional assays, which we will describe and summarize.
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Cite this article as:
Drenkhahn K. Sara, Jackson A. Glenn, Slusarz Anna, Starkey J.E. Nicholas and Lubahn B. Dennis, Inhibition of Hedgehog/Gli Signaling by Botanicals: A Review of Compounds with Potential Hedgehog Pathway Inhibitory Activities, Current Cancer Drug Targets 2013; 13 (5) . https://dx.doi.org/10.2174/15680096113139990003
DOI https://dx.doi.org/10.2174/15680096113139990003 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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