Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

Peng Liu, Wei Wang, Zhigang Zhou, Andrew J O Smith, Richard P Bowater, Ian Michael Wormstone, Yuqiong Chen, Yongping Bao (Corresponding Author)

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Sulforaphane (SFN) exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs) and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H₂O₂ challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the induction of intracellular glutathione (GSH) played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

Original languageEnglish
Article number585
JournalNutrients
Volume10
Issue number5
DOIs
Publication statusPublished - 9 May 2018

Fingerprint

Hep G2 Cells
hepatoma
Hepatocellular Carcinoma
metabolites
cells
cell movement
DNA damage
cell viability
glutathione
DNA Damage
Cell Movement
Glutathione
Cell Survival
acetylcysteine
chemoprevention
NF-E2-Related Factor 2
Antioxidant Response Elements
sulforafan
response elements
tissue distribution

Keywords

  • Acetylcysteine/metabolism
  • Anticarcinogenic Agents/pharmacology
  • Antioxidant Response Elements/drug effects
  • Cell Adhesion/drug effects
  • Cell Movement/drug effects
  • Cell Survival/drug effects
  • Comet Assay
  • DNA Damage/drug effects
  • Dose-Response Relationship, Drug
  • Glutathione/metabolism
  • Hep G2 Cells
  • Human Umbilical Vein Endothelial Cells/drug effects
  • Humans
  • Hydrogen Peroxide/toxicity
  • Isothiocyanates/pharmacology
  • NF-E2-Related Factor 2/genetics
  • Sulforaphane
  • Chemoprevention
  • Sulforaphane metabolites
  • Nrf2
  • GSH

Cite this

Liu, P., Wang, W., Zhou, Z., Smith, A. J. O., Bowater, R. P., Wormstone, I. M., ... Bao, Y. (2018). Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells. Nutrients, 10(5), [585]. https://doi.org/10.3390/nu10050585

Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells. / Liu, Peng; Wang, Wei; Zhou, Zhigang; Smith, Andrew J O; Bowater, Richard P; Wormstone, Ian Michael; Chen, Yuqiong; Bao, Yongping (Corresponding Author).

In: Nutrients, Vol. 10, No. 5, 585, 09.05.2018.

Research output: Contribution to journalArticle

Liu, P, Wang, W, Zhou, Z, Smith, AJO, Bowater, RP, Wormstone, IM, Chen, Y & Bao, Y 2018, 'Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells', Nutrients, vol. 10, no. 5, 585. https://doi.org/10.3390/nu10050585
Liu, Peng ; Wang, Wei ; Zhou, Zhigang ; Smith, Andrew J O ; Bowater, Richard P ; Wormstone, Ian Michael ; Chen, Yuqiong ; Bao, Yongping. / Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells. In: Nutrients. 2018 ; Vol. 10, No. 5.
@article{506be0d974cc4100818b0d1de2a580b9,
title = "Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells",
abstract = "Sulforaphane (SFN) exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs) and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H₂O₂ challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the induction of intracellular glutathione (GSH) played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.",
keywords = "Acetylcysteine/metabolism, Anticarcinogenic Agents/pharmacology, Antioxidant Response Elements/drug effects, Cell Adhesion/drug effects, Cell Movement/drug effects, Cell Survival/drug effects, Comet Assay, DNA Damage/drug effects, Dose-Response Relationship, Drug, Glutathione/metabolism, Hep G2 Cells, Human Umbilical Vein Endothelial Cells/drug effects, Humans, Hydrogen Peroxide/toxicity, Isothiocyanates/pharmacology, NF-E2-Related Factor 2/genetics, Sulforaphane, Chemoprevention, Sulforaphane metabolites, Nrf2, GSH",
author = "Peng Liu and Wei Wang and Zhigang Zhou and Smith, {Andrew J O} and Bowater, {Richard P} and Wormstone, {Ian Michael} and Yuqiong Chen and Yongping Bao",
year = "2018",
month = "5",
day = "9",
doi = "10.3390/nu10050585",
language = "English",
volume = "10",
journal = "Nutrients",
issn = "2072-6643",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",

}

TY - JOUR

T1 - Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

AU - Liu, Peng

AU - Wang, Wei

AU - Zhou, Zhigang

AU - Smith, Andrew J O

AU - Bowater, Richard P

AU - Wormstone, Ian Michael

AU - Chen, Yuqiong

AU - Bao, Yongping

PY - 2018/5/9

Y1 - 2018/5/9

N2 - Sulforaphane (SFN) exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs) and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H₂O₂ challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the induction of intracellular glutathione (GSH) played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

AB - Sulforaphane (SFN) exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs) and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H₂O₂ challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the induction of intracellular glutathione (GSH) played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

KW - Acetylcysteine/metabolism

KW - Anticarcinogenic Agents/pharmacology

KW - Antioxidant Response Elements/drug effects

KW - Cell Adhesion/drug effects

KW - Cell Movement/drug effects

KW - Cell Survival/drug effects

KW - Comet Assay

KW - DNA Damage/drug effects

KW - Dose-Response Relationship, Drug

KW - Glutathione/metabolism

KW - Hep G2 Cells

KW - Human Umbilical Vein Endothelial Cells/drug effects

KW - Humans

KW - Hydrogen Peroxide/toxicity

KW - Isothiocyanates/pharmacology

KW - NF-E2-Related Factor 2/genetics

KW - Sulforaphane

KW - Chemoprevention

KW - Sulforaphane metabolites

KW - Nrf2

KW - GSH

U2 - 10.3390/nu10050585

DO - 10.3390/nu10050585

M3 - Article

C2 - 29747418

VL - 10

JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 5

M1 - 585

ER -