Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell growth through the induction of ERK1/2-mediated apoptosis.
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.
Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
Ming-Wei
MW
Lin
An-Shen
AS
Lin
Deng-Chyang
DC
Wu
Sophie S W
SS
Wang
Fang-Rong
FR
Chang
Yang-Chang
YC
Wu
Yaw-Bin
YB
Huang
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C534699:CCNB1 protein, human; C436291:CDKN1B protein, human; D056744:Cyclin B1; D051028:bcl-2-Associated X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D007810:Lanosterol; C062557:euphol; C505407:CASP3 protein, human; D053148:Caspase 3