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      Inhibition of Hedgehog-Signaling Driven Genes in Prostate Cancer Cells by Sutherlandia frutescens Extract

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          Abstract

          Sutherlandia frutescens (L) R. Br. (Sutherlandia) is a South African botanical that is traditionally used to treat a variety of health conditions, infections and diseases, including cancer. We hypothesized Sutherlandia might act through Gli/ Hedgehog (Hh)-signaling in prostate cancer cells and used RNA-Seq transcription profiling to profile gene expression in TRAMPC2 murine prostate cancer cells with or without Sutherlandia extracts. We found 50% of Hh-responsive genes can be repressed by Sutherlandia ethanol extract, including the canonical Hh-responsive genes Gli1 and Ptch1 as well as newly distinguished Hh-responsive genes Hsd11b1 and Penk.

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          featureCounts: An efficient general-purpose program for assigning sequence reads to genomic features

          , , (2013)
          Next-generation sequencing technologies generate millions of short sequence reads, which are usually aligned to a reference genome. In many applications, the key information required for downstream analysis is the number of reads mapping to each genomic feature, for example to each exon or each gene. The process of counting reads is called read summarization. Read summarization is required for a great variety of genomic analyses but has so far received relatively little attention in the literature. We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments. featureCounts implements highly efficient chromosome hashing and feature blocking techniques. It is considerably faster than existing methods (by an order of magnitude for gene-level summarization) and requires far less computer memory. It works with either single or paired-end reads and provides a wide range of options appropriate for different sequencing applications. featureCounts is available under GNU General Public License as part of the Subread (http://subread.sourceforge.net) or Rsubread (http://www.bioconductor.org) software packages.
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            Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours.

            David Berman, Sunil S. Karhadkar, Anirban Maitra … (2003)
            Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlin's syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlin's syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.
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              Hedgehog signalling in prostate regeneration, neoplasia and metastasis.

              Sunil S. Karhadkar, G. Bova, Nadia Abdallah … (2004)
              Metastatic cancers adopt certain properties of normal cells in developing or regenerating organs, such as the ability to proliferate and alter tissue organization. We find here that activity of the Hedgehog (Hh) signalling pathway, which has essential roles in developmental patterning, is required for regeneration of prostate epithelium, and that continuous pathway activation transforms prostate progenitor cells and renders them tumorigenic. Elevated pathway activity furthermore distinguishes metastatic from localized prostate cancer, and pathway manipulation can modulate invasiveness and metastasis. Pathway activity is triggered in response to endogenous expression of Hh ligands, and is dependent upon the expression of Smoothened, an essential Hh response component that is not expressed in benign prostate epithelial cells. Monitoring and manipulating Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential.
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                Author and article information

                Contributors
                Rajeev Samant: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 28 December 2015
                Publication date Collection: 2015
                Volume: 10
                Issue: 12
                Electronic Location Identifier: e0145507
                Affiliations
                [1 ]Department of Biochemistry, University of Missouri, Columbia, MO 65211, United States of America
                [2 ]MU Center for Botanical Interaction Studies, University of Missouri, Columbia, MO 65211, United States of America
                [3 ]Division of Animal Science, University of Missouri, Columbia, MO 65211, United States of America
                [4 ]Computer Science Department, University of Missouri, Columbia, MO 65211, United States of America
                [5 ]Informatics Institute, University of Missouri, Columbia, MO 65211, United States of America
                [6 ]Xiphophorus Genetic Stock Center, Texas State University, San Marcos, TX 78666, United States of America
                University of Alabama at Birmingham, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: YL NS WRF DBL. Performed the experiments: YL NS JL. Analyzed the data: YL. Contributed reagents/materials/analysis tools: JC WL DBL. Wrote the paper: YL WRF DBL.

                Article
                Publisher ID: PONE-D-15-44553
                DOI: 10.1371/journal.pone.0145507
                PMC ID: 4694108
                PubMed ID: 26710108
                SO-VID: bcb82be2-be73-413b-9a35-55e47aec79d0
                Copyright © © 2015 Lu et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                Date received : 9 October 2015
                Date accepted : 4 December 2015
                Page count
                Figures: 3, Tables: 0, Pages: 9
                Funding
                This publication or project was made possible in part by Grant Number P50AT006273 from the National Center for Complementary and Integrative Health (NCCIH), the Office of Dietary Supplements (ODS), and the National Cancer Institute (NCI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Custom metadata
                Data Availability The dataset is stored in NCBI-GEO, the accession number is GSE75760.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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