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

Lu, Yuan; Starkey, Nicholas J.E.; W, Lei; Li, Jilong; Cheng, Jianlin; Folk, William R.; Lubahn, Dennis B.

doi:10.1371/journal.pone.0145507

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…The mechanisms for these putative medicinal properties of S. frutescens have not been investigated extensively. We and others have reported that ethanolic and aqueous extracts of this plant possess anti-inflammatory and immuno-stimulatory activities, respectively 6,7 .…”

Section: Introductionmentioning

confidence: 88%

“…However, the mechanism(s) by which S. frutescens may modulate health outcomes remains unclear. Recently, our group demonstrated that an ethanol extract of S. frutescens down-regulated 50% of Hedgehog-responsive genes in murine prostate cancer cells (i.e., TRAMPC2) 6 . Also, we have previously reported that extracts from Sutherlandia can diminish NF-κB, ERK, AP-1, and JAK-STAT1 signaling in macrophages and microglia cells [8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

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RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>

W¹,

Lu²,

Hou³

et al. 2018

Preprint

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Sutherlandia frutescens (S. frutescens) has been traditionally used as an herbal medicine to ameliorate symptoms associated with cancer, infectious diseases, as well as inflammation. The objective of this investigation was to explore the impact of S. frutescens on the expression of genes in a murine macrophage cell line (i.e., RAW 264.7). We found that treatment with an ethanolic-extract of S. frutescens (SFE) 1 h prior to the stimulation with LPS and IFNγ for 24 h significantly affected the expression of 715 genes in RAW 264.7 cells. When the post-stimulation period was shortened to 8 h, the number of genes that were significantly impacted by SFE diminished to 50. Pathway analysis revealed that inflammatory signaling pathways, such as NF-κB, MAPK, and TNF, as well as signaling pathways associated with immune-related responses, were inhibited by SFE treatment. These findings are consistent with previously reported anti-inflammatory activity of SFE and enable better understanding of the immune-modulating properties of this botanical. To our knowledge, this represents the first report on the impact of S. frutescens on global gene expression in an immune cell population.

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Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>

W¹,

Lu²,

Hou³

et al. 2018

Preprint

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“…The short filtered sequencing reads that were acquired were mapped to the human genome by the TopHat2 and Subreads package; the featureCounts function was used to quantify the gene expression values. These gene expression values were then used to calculate the size of the library and dataset dispersion for the analysis of differentially expressed genes [15]. Differential gene expression was examined using the R/Bioconductor package edgeR and established by log fold change (LogFC) and false discovery rate (FDR) (LogFC ≥ 1 or ≤-1; FDR ≤ 0.05).…”

Section: Methodsmentioning

confidence: 99%

Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line

Hasan

Razvi

Choudhry

et al. 2019

Analytical Cellular Pathology

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Human hepatocellular carcinoma (HCC) is the most common and recurrent type of primary adult liver cancer without any effective therapy. Plant-derived compounds acting as anticancer agents can induce apoptosis by targeting several signaling pathways. Strigolactone (SL) is a novel class of phytohormone, whose analogues have been reported to possess anticancer properties on a panel of human cancer cell lines through inducing cell cycle arrest, destabilizing microtubular integrity, reducing damaged in the DNA repair machinery, and inducing apoptosis. In our previous study, we reported that a novel SL analogue, TIT3, reduces HepG2 cell proliferation, inhibits cell migration, and induces apoptosis. To decipher the mechanisms of TIT3-induced anticancer activity in HepG2, we performed RNA sequencing and the differential expression of genes was analyzed using different tools. RNA-Seq data showed that the genes responsible for microtubule organization such as TUBB, BUB1B, TUBG2, TUBGCP6, TPX2, and MAP7 were significantly downregulated. Several epigenetic modulators such as UHRF1, HDAC7, and DNMT1 were also considerably downregulated, and this effect was associated with significant upregulation of various proapoptotic genes including CASP3, TNF-α, CASP7, and CDKN1A (p21). Likewise, damaged DNA repair genes such as RAD51, RAD52, and DDB2 were also significantly downregulated. This study indicates that TIT3-induced antiproliferative and proapoptotic activities on HCC cells could involve several signaling pathways. Our results suggest that TIT3 might be a promising drug to treat HCC.

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“…Extracts of S. frutescens have shown antiproliferation and apoptotic effect in breast cancer cells and cervical cancer cells [ 180 – 182 ]. Its actual mechanism of action remains largely unknown but in vitro Sutherlandia represses Hedgehog-signaling pathway in murine prostate cancer cells [ 183 ] as well as key molecules in the PI-3 K pathway in colon cancer cells [ 184 ].…”

Section: African Herbs Used For Common Ncds Modulating Cyp450 or Pmentioning

confidence: 99%

Cytochrome P450 and P‐Glycoprotein‐Mediated Interactions Involving African Herbs Indicated for Common Noncommunicable Diseases

Ondieki

Nyagblordzro

Kikete

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Herbal remedies are regularly used to complement conventional therapies in the treatment of various illnesses in Africa. This may be because they are relatively cheap and easily accessible and are believed by many to be safe, cause fewer side effects, and are less likely to cause dependency. On the contrary, many herbs have been shown to alter the pharmacokinetics of coadministered allopathic medicines and can either synergize or antagonize therapeutic effects as well as altering the toxicity profiles of these drugs. Current disease burden data point towards epidemiological transitions characterised by increasing urbanization and changing lifestyles, risk factors for chronic diseases like hypertension, diabetes, and cancer which often present as multimorbidities. As a result, we highlight African herb-drug interactions (HDIs) modulated via cytochrome P450 enzyme family (CYP) and P-glycoprotein (P-gp) and the consequences thereof in relation to antihypertensive, antidiabetic, and anticancer drugs. CYPs are enzymes which account for to up to 70% of drug metabolism while P-gp is an efflux pump that extrudes drug substrates out of cells. Consequently, regulation of the relative activity of both CYP and P-gp by African herbs influences the effective drug concentration at the site of action and modifies therapeutic outcomes.

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

Cited by 8 publications

References 37 publications

RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>

RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>

Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line

Cytochrome P450 and P‐Glycoprotein‐Mediated Interactions Involving African Herbs Indicated for Common Noncommunicable Diseases

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

Cited by 8 publications

References 37 publications

RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia&nbsp;frutescens</em>

RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia&nbsp;frutescens</em>

Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line

Cytochrome P450 and P‐Glycoprotein‐Mediated Interactions Involving African Herbs Indicated for Common Noncommunicable Diseases

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Product

Resources

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RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>

RNA Sequence Analysis Reveals Expected and Novel Immuno-Modulatory Activities by <em>Sutherlandia frutescens</em>