title: Anti-tumor activity of the X-linked inhibitor of apoptosis (XIAP) inhibitor embelin in gastric cancer cells.
abstract: This study investigated the anticancer effects of embelin in human gastric cancer cells and the underlying molecular mechanisms. Gastric cancer cells were treated with embelin and 5-FU for methyl-thiazolyl-tetrazolium bromide cell viability assay and flow cytometric detection of cell viability and apoptosis. Protein pathway array (PPA) and Western blot were used to investigate differentially expressed proteins in embelin-treated gastric cancer cells. Embelin reduced gastric cancer cell viability, induced apoptosis, and enhanced 5-FU antitumor activity in gastric cancer cells. Mechanistically, embelin induced cell cycle arrest at the S and G2/M phases. Molecularly, embelin downregulated expression of X-linked inhibitor of apoptosis and cell cycle-regulatory proteins, such as CDK1, CDC25B, CDC25C, cyclinB1, and CDK2. PPA analysis showed that embelin modulated several pathways that are associated with cell growth and apoptosis, such as PI3K/AKT, JAK/STAT, p38 MAPK, and p53. The data from the current study implied that reduction of gastric cancer cell viability after treatment with embelin was through cell cycle arrest at the S and G2/M phases and apoptosis.
authors.affiliation: Department of General Surgery, The First Hospital, Jilin University, Changchun, 130021, Jilin, China.
authors.forename: Da-Guang
authors.initials: DG
authors.lastname: Wang
authors.forename: Ya-Bin
authors.initials: YB
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Punyaram
authors.initials: P
authors.lastname: Kharbuja
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: David Y
authors.initials: DY
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Suo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors*
chemical_list: D016227:Benzoquinones; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C010945:embelin; D005472:Fluorouracil