Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell growth through the induction of ERK1/2-mediated apoptosis

Ming-Wei Lin; An-Shen Lin; Deng-Chyang Wu; Sophie S W Wang; Fang-Rong Chang; Yang-Chang Wu; Yaw-Bin Huang

doi:10.1016/j.fct.2012.05.029

Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell growth through the induction of ERK1/2-mediated apoptosis

Food Chem Toxicol. 2012 Dec;50(12):4333-9. doi: 10.1016/j.fct.2012.05.029. Epub 2012 May 23.

Authors

Ming-Wei Lin¹, An-Shen Lin, Deng-Chyang Wu, Sophie S W Wang, Fang-Rong Chang, Yang-Chang Wu, Yaw-Bin Huang

Affiliation

¹ Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.

PMID: 22634261
DOI: 10.1016/j.fct.2012.05.029

Abstract

Gastric cancer is one of the most common malignancies worldwide, and the main cause of cancer-related death in Asia. The present study assessed the anticancer effects of euphol, a triterpene alcohol with anti-inflammatory and antiviral activities on human gastric cancer cells. Euphol showed higher cytotoxicity activity against human gastric CS12 cancer cells than against noncancer CSN cells. In addition, it up-regulated the pro-apoptotic protein BAX and down-regulated the prosurvival protein Bcl-2, causing mitochondrial dysfunction, possibly by caspase-3 activation. The anti-proliferative effects of euphol were associated with the increased p27(kip1) levels and decreased cyclin B1 levels. Inhibition of ERK1/2 activation by PD98059 reversed euphol-induced pro-apoptotic protein expression and cell death. Taken together, these findings suggest that euphol selectively induced gastric cancer cells apoptosis by modulation of ERK signaling, and could thus be of value for cancer therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects*
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism
Caspase 3 / genetics
Caspase 3 / metabolism
Cell Death / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin B1 / genetics
Cyclin B1 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / genetics
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Down-Regulation
Euphorbia / chemistry*
Humans
Lanosterol / analogs & derivatives*
Lanosterol / pharmacology
MAP Kinase Signaling System / drug effects*
Mitochondria / drug effects
Mitochondria / metabolism
Phosphorylation
Signal Transduction
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology
Up-Regulation
bcl-2-Associated X Protein / genetics
bcl-2-Associated X Protein / metabolism

Substances

Apoptosis Regulatory Proteins
BAX protein, human
CCNB1 protein, human
CDKN1B protein, human
Cyclin B1
bcl-2-Associated X Protein
Cyclin-Dependent Kinase Inhibitor p27
Lanosterol
euphol
CASP3 protein, human
Caspase 3