Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway

Che Yuan Hu, Hung Tsung Wu, Yu Chu Su, Ching Han Lin, Chih Jen Chang, Chao Liang Wu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Evodiamine is one of the main components isolated from Evodia rutaecarpa, and it has been reported to exert inhibitory effects on cancers by anti-proliferative and apoptosis-inducing activities. Although the anti-cancer activity of evodiamine has been identified, the precise mechanisms of this action remain obscure. While previous studies indicated that evodiamine exerts anti-tumor effects through inhibiting β-catenin activity, and WW domain-containing oxidoreductase (WWOX) regulates β-catenin accumulation in cytoplasm, the effects of evodiamine on the expression of WWOX are still unknown. In this study, we provide evidence that evodiamine dose- and time-dependently inhibits both Mus musculus and Homo sapiens hepatocellular carcinoma (HCC) cells, as well as Hepa1-6 and HepG2 cell proliferation. We further tested the therapeutic effects of evodiamine in Hepa1-6 hepatoma-bearing mice, and we found that treatment of evodiamine by oral gavage significantly decreased the tumor size of the mice. Moreover, the expressions of WWOX were dose-dependently increased in HCC cell lines as well as in Hepa1-6 hepatoma-bearing mice after the treatment with evodiamine. Knockdown of WWOX in HepG2 and Hepa1-6 cells diminished the effects of evodiamine on the inhibitory effect of cancer cell growth, indicating that evodiamine induced anti-cancer activity through a WWOX-dependent pathway. As such, evodiamine activated WWOX to exert an anti-HCC activity, and might be a potential therapeutic or preventive candidate for HCC treatment.

Original languageEnglish
JournalMolecules (Basel, Switzerland)
Volume22
Issue number7
DOIs
Publication statusPublished - Jul 14 2017
Externally publishedYes

Fingerprint

Hepatocellular Carcinoma
cancer
mice
Bearings (structural)
Catenins
Neoplasms
tumors
dosage
Tumors
Evodia
evodiamine
cytoplasm
apoptosis
Cells
cultured cells
Hep G2 Cells
Cell proliferation
Cell growth
Therapeutic Uses
Oxidoreductases

Keywords

  • Evodia rutaecarpa
  • evodiamine
  • hepatocellular carcinoma
  • herbal medicine
  • WW domain-containing oxidoreductase

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway. / Hu, Che Yuan; Wu, Hung Tsung; Su, Yu Chu; Lin, Ching Han; Chang, Chih Jen; Wu, Chao Liang.

In: Molecules (Basel, Switzerland), Vol. 22, No. 7, 14.07.2017.

Research output: Contribution to journalArticle

Hu, Che Yuan ; Wu, Hung Tsung ; Su, Yu Chu ; Lin, Ching Han ; Chang, Chih Jen ; Wu, Chao Liang. / Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway. In: Molecules (Basel, Switzerland). 2017 ; Vol. 22, No. 7.
@article{5009312dd0374cbcbf545d9b02953b48,
title = "Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway",
abstract = "Evodiamine is one of the main components isolated from Evodia rutaecarpa, and it has been reported to exert inhibitory effects on cancers by anti-proliferative and apoptosis-inducing activities. Although the anti-cancer activity of evodiamine has been identified, the precise mechanisms of this action remain obscure. While previous studies indicated that evodiamine exerts anti-tumor effects through inhibiting β-catenin activity, and WW domain-containing oxidoreductase (WWOX) regulates β-catenin accumulation in cytoplasm, the effects of evodiamine on the expression of WWOX are still unknown. In this study, we provide evidence that evodiamine dose- and time-dependently inhibits both Mus musculus and Homo sapiens hepatocellular carcinoma (HCC) cells, as well as Hepa1-6 and HepG2 cell proliferation. We further tested the therapeutic effects of evodiamine in Hepa1-6 hepatoma-bearing mice, and we found that treatment of evodiamine by oral gavage significantly decreased the tumor size of the mice. Moreover, the expressions of WWOX were dose-dependently increased in HCC cell lines as well as in Hepa1-6 hepatoma-bearing mice after the treatment with evodiamine. Knockdown of WWOX in HepG2 and Hepa1-6 cells diminished the effects of evodiamine on the inhibitory effect of cancer cell growth, indicating that evodiamine induced anti-cancer activity through a WWOX-dependent pathway. As such, evodiamine activated WWOX to exert an anti-HCC activity, and might be a potential therapeutic or preventive candidate for HCC treatment.",
keywords = "Evodia rutaecarpa, evodiamine, hepatocellular carcinoma, herbal medicine, WW domain-containing oxidoreductase",
author = "Hu, {Che Yuan} and Wu, {Hung Tsung} and Su, {Yu Chu} and Lin, {Ching Han} and Chang, {Chih Jen} and Wu, {Chao Liang}",
year = "2017",
month = "7",
day = "14",
doi = "10.3390/molecules22071175",
language = "English",
volume = "22",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "7",

}

TY - JOUR

T1 - Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway

AU - Hu, Che Yuan

AU - Wu, Hung Tsung

AU - Su, Yu Chu

AU - Lin, Ching Han

AU - Chang, Chih Jen

AU - Wu, Chao Liang

PY - 2017/7/14

Y1 - 2017/7/14

N2 - Evodiamine is one of the main components isolated from Evodia rutaecarpa, and it has been reported to exert inhibitory effects on cancers by anti-proliferative and apoptosis-inducing activities. Although the anti-cancer activity of evodiamine has been identified, the precise mechanisms of this action remain obscure. While previous studies indicated that evodiamine exerts anti-tumor effects through inhibiting β-catenin activity, and WW domain-containing oxidoreductase (WWOX) regulates β-catenin accumulation in cytoplasm, the effects of evodiamine on the expression of WWOX are still unknown. In this study, we provide evidence that evodiamine dose- and time-dependently inhibits both Mus musculus and Homo sapiens hepatocellular carcinoma (HCC) cells, as well as Hepa1-6 and HepG2 cell proliferation. We further tested the therapeutic effects of evodiamine in Hepa1-6 hepatoma-bearing mice, and we found that treatment of evodiamine by oral gavage significantly decreased the tumor size of the mice. Moreover, the expressions of WWOX were dose-dependently increased in HCC cell lines as well as in Hepa1-6 hepatoma-bearing mice after the treatment with evodiamine. Knockdown of WWOX in HepG2 and Hepa1-6 cells diminished the effects of evodiamine on the inhibitory effect of cancer cell growth, indicating that evodiamine induced anti-cancer activity through a WWOX-dependent pathway. As such, evodiamine activated WWOX to exert an anti-HCC activity, and might be a potential therapeutic or preventive candidate for HCC treatment.

AB - Evodiamine is one of the main components isolated from Evodia rutaecarpa, and it has been reported to exert inhibitory effects on cancers by anti-proliferative and apoptosis-inducing activities. Although the anti-cancer activity of evodiamine has been identified, the precise mechanisms of this action remain obscure. While previous studies indicated that evodiamine exerts anti-tumor effects through inhibiting β-catenin activity, and WW domain-containing oxidoreductase (WWOX) regulates β-catenin accumulation in cytoplasm, the effects of evodiamine on the expression of WWOX are still unknown. In this study, we provide evidence that evodiamine dose- and time-dependently inhibits both Mus musculus and Homo sapiens hepatocellular carcinoma (HCC) cells, as well as Hepa1-6 and HepG2 cell proliferation. We further tested the therapeutic effects of evodiamine in Hepa1-6 hepatoma-bearing mice, and we found that treatment of evodiamine by oral gavage significantly decreased the tumor size of the mice. Moreover, the expressions of WWOX were dose-dependently increased in HCC cell lines as well as in Hepa1-6 hepatoma-bearing mice after the treatment with evodiamine. Knockdown of WWOX in HepG2 and Hepa1-6 cells diminished the effects of evodiamine on the inhibitory effect of cancer cell growth, indicating that evodiamine induced anti-cancer activity through a WWOX-dependent pathway. As such, evodiamine activated WWOX to exert an anti-HCC activity, and might be a potential therapeutic or preventive candidate for HCC treatment.

KW - Evodia rutaecarpa

KW - evodiamine

KW - hepatocellular carcinoma

KW - herbal medicine

KW - WW domain-containing oxidoreductase

UR - http://www.scopus.com/inward/record.url?scp=85044020465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044020465&partnerID=8YFLogxK

U2 - 10.3390/molecules22071175

DO - 10.3390/molecules22071175

M3 - Article

C2 - 28708106

AN - SCOPUS:85044020465

VL - 22

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 7

ER -