Polyphenol extracts from dried sugarcane inhibit inflammatory mediators in an in vitro colon cancer model

Daniel Bucio-Noble, Liisa Kautto, Christoph Krisp, Malcolm S. Ball, Mark P. Molloy

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Sugarcane is an important crop grown in tropical regions for sugar, and for ethanol production. Sugarcane is also a source of phytochemicals but its nutraceutical potential has been under-explored. We show that ethanol extracts of whole dried sugarcane (WDS) recovers a rich content of polyphenols, flavonoids and antioxidant activity that act on inflammatory mediator proteins. To investigate the mechanisms of this activity, we stimulated SW480 colon cancer cells with lipopolysaccharide, exposed cells to WDS and quantitated changes to the proteome and phosphoproteome using label-free mass spectrometry. The grape-derived anti-inflammatory polyphenol, resveratrol (RSV) was used as a control. Using SWATH-MS we quantitated ~3000 proteins showing that WDS significantly altered the expression of the oxidative stress regulator SELH. WDS induced changes in protein expression predicted the involvement of NFκB pathway members. Reduced NFκB phosphorylation and IL-8 secretion confirmed this effect. In contrast, RSV was predicted to act primarily through modulation of the PI3K/AKT pathway. Phosphoproteomics studies indicate that WDS interfered in the phosphorylation of cell stress regulators c-Jun, EGFR, PKA, PKCβ and SIRT1. Confirmed through pharmacological inhibition, kinase enrichment analysis presented C-Raf to modulate WDS activity. These results demonstrate the anti-inflammatory utility of WSD and define aspects of its mechanisms of action. Significance: Despite the increasing interest of nutraceuticals in health promotion, scientific evidence proving the molecular mechanisms involved is still lacking. This study investigated some of the mechanistic aspects of in vitro use of whole dried sugarcane extracts in the context of regulating cellular inflammation by using proteomics and phosphoproteomics strategies. We determined that WDS extracts regulate key inflammatory pathways including NFκB, while kinase enrichment analysis from phosphoproteomics demonstrated a role for C-Raf in controlling this mechanism. We demonstrated that the mechanism of WDS extracts on controlling inflammation differs from that of the polyphenol, resveratrol. The results presented herein contribute towards unravelling the activity of nutraceuticals extracted from sugarcane.

LanguageEnglish
Pages1-10
Number of pages10
JournalJournal of Proteomics
Volume177
DOIs
Publication statusPublished - 15 Apr 2018

Fingerprint

Saccharum
Polyphenols
Colonic Neoplasms
Phosphorylation
Anti-Inflammatory Agents
Ethanol
Phosphotransferases
Proteins
Oxidative stress
Phytochemicals
Proteome
Interleukin-8
Phosphatidylinositol 3-Kinases
Flavonoids
Sugars
Crops
Mass spectrometry
Lipopolysaccharides
Labels
Dietary Supplements

Keywords

  • NFκB
  • phosphoproteomics
  • polyphenols
  • proteomics
  • resveratrol
  • sugarcane

Cite this

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title = "Polyphenol extracts from dried sugarcane inhibit inflammatory mediators in an in vitro colon cancer model",
abstract = "Sugarcane is an important crop grown in tropical regions for sugar, and for ethanol production. Sugarcane is also a source of phytochemicals but its nutraceutical potential has been under-explored. We show that ethanol extracts of whole dried sugarcane (WDS) recovers a rich content of polyphenols, flavonoids and antioxidant activity that act on inflammatory mediator proteins. To investigate the mechanisms of this activity, we stimulated SW480 colon cancer cells with lipopolysaccharide, exposed cells to WDS and quantitated changes to the proteome and phosphoproteome using label-free mass spectrometry. The grape-derived anti-inflammatory polyphenol, resveratrol (RSV) was used as a control. Using SWATH-MS we quantitated ~3000 proteins showing that WDS significantly altered the expression of the oxidative stress regulator SELH. WDS induced changes in protein expression predicted the involvement of NFκB pathway members. Reduced NFκB phosphorylation and IL-8 secretion confirmed this effect. In contrast, RSV was predicted to act primarily through modulation of the PI3K/AKT pathway. Phosphoproteomics studies indicate that WDS interfered in the phosphorylation of cell stress regulators c-Jun, EGFR, PKA, PKCβ and SIRT1. Confirmed through pharmacological inhibition, kinase enrichment analysis presented C-Raf to modulate WDS activity. These results demonstrate the anti-inflammatory utility of WSD and define aspects of its mechanisms of action. Significance: Despite the increasing interest of nutraceuticals in health promotion, scientific evidence proving the molecular mechanisms involved is still lacking. This study investigated some of the mechanistic aspects of in vitro use of whole dried sugarcane extracts in the context of regulating cellular inflammation by using proteomics and phosphoproteomics strategies. We determined that WDS extracts regulate key inflammatory pathways including NFκB, while kinase enrichment analysis from phosphoproteomics demonstrated a role for C-Raf in controlling this mechanism. We demonstrated that the mechanism of WDS extracts on controlling inflammation differs from that of the polyphenol, resveratrol. The results presented herein contribute towards unravelling the activity of nutraceuticals extracted from sugarcane.",
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Polyphenol extracts from dried sugarcane inhibit inflammatory mediators in an in vitro colon cancer model. / Bucio-Noble, Daniel; Kautto, Liisa; Krisp, Christoph; Ball, Malcolm S.; Molloy, Mark P.

In: Journal of Proteomics, Vol. 177, 15.04.2018, p. 1-10.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Polyphenol extracts from dried sugarcane inhibit inflammatory mediators in an in vitro colon cancer model

AU - Bucio-Noble,Daniel

AU - Kautto,Liisa

AU - Krisp,Christoph

AU - Ball,Malcolm S.

AU - Molloy,Mark P.

PY - 2018/4/15

Y1 - 2018/4/15

N2 - Sugarcane is an important crop grown in tropical regions for sugar, and for ethanol production. Sugarcane is also a source of phytochemicals but its nutraceutical potential has been under-explored. We show that ethanol extracts of whole dried sugarcane (WDS) recovers a rich content of polyphenols, flavonoids and antioxidant activity that act on inflammatory mediator proteins. To investigate the mechanisms of this activity, we stimulated SW480 colon cancer cells with lipopolysaccharide, exposed cells to WDS and quantitated changes to the proteome and phosphoproteome using label-free mass spectrometry. The grape-derived anti-inflammatory polyphenol, resveratrol (RSV) was used as a control. Using SWATH-MS we quantitated ~3000 proteins showing that WDS significantly altered the expression of the oxidative stress regulator SELH. WDS induced changes in protein expression predicted the involvement of NFκB pathway members. Reduced NFκB phosphorylation and IL-8 secretion confirmed this effect. In contrast, RSV was predicted to act primarily through modulation of the PI3K/AKT pathway. Phosphoproteomics studies indicate that WDS interfered in the phosphorylation of cell stress regulators c-Jun, EGFR, PKA, PKCβ and SIRT1. Confirmed through pharmacological inhibition, kinase enrichment analysis presented C-Raf to modulate WDS activity. These results demonstrate the anti-inflammatory utility of WSD and define aspects of its mechanisms of action. Significance: Despite the increasing interest of nutraceuticals in health promotion, scientific evidence proving the molecular mechanisms involved is still lacking. This study investigated some of the mechanistic aspects of in vitro use of whole dried sugarcane extracts in the context of regulating cellular inflammation by using proteomics and phosphoproteomics strategies. We determined that WDS extracts regulate key inflammatory pathways including NFκB, while kinase enrichment analysis from phosphoproteomics demonstrated a role for C-Raf in controlling this mechanism. We demonstrated that the mechanism of WDS extracts on controlling inflammation differs from that of the polyphenol, resveratrol. The results presented herein contribute towards unravelling the activity of nutraceuticals extracted from sugarcane.

AB - Sugarcane is an important crop grown in tropical regions for sugar, and for ethanol production. Sugarcane is also a source of phytochemicals but its nutraceutical potential has been under-explored. We show that ethanol extracts of whole dried sugarcane (WDS) recovers a rich content of polyphenols, flavonoids and antioxidant activity that act on inflammatory mediator proteins. To investigate the mechanisms of this activity, we stimulated SW480 colon cancer cells with lipopolysaccharide, exposed cells to WDS and quantitated changes to the proteome and phosphoproteome using label-free mass spectrometry. The grape-derived anti-inflammatory polyphenol, resveratrol (RSV) was used as a control. Using SWATH-MS we quantitated ~3000 proteins showing that WDS significantly altered the expression of the oxidative stress regulator SELH. WDS induced changes in protein expression predicted the involvement of NFκB pathway members. Reduced NFκB phosphorylation and IL-8 secretion confirmed this effect. In contrast, RSV was predicted to act primarily through modulation of the PI3K/AKT pathway. Phosphoproteomics studies indicate that WDS interfered in the phosphorylation of cell stress regulators c-Jun, EGFR, PKA, PKCβ and SIRT1. Confirmed through pharmacological inhibition, kinase enrichment analysis presented C-Raf to modulate WDS activity. These results demonstrate the anti-inflammatory utility of WSD and define aspects of its mechanisms of action. Significance: Despite the increasing interest of nutraceuticals in health promotion, scientific evidence proving the molecular mechanisms involved is still lacking. This study investigated some of the mechanistic aspects of in vitro use of whole dried sugarcane extracts in the context of regulating cellular inflammation by using proteomics and phosphoproteomics strategies. We determined that WDS extracts regulate key inflammatory pathways including NFκB, while kinase enrichment analysis from phosphoproteomics demonstrated a role for C-Raf in controlling this mechanism. We demonstrated that the mechanism of WDS extracts on controlling inflammation differs from that of the polyphenol, resveratrol. The results presented herein contribute towards unravelling the activity of nutraceuticals extracted from sugarcane.

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