title: Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling.
abstract: Caudatin has been reported to trigger apoptosis in several types of cancer cell lines. In the present study, we investigated whether caudatin has therapeutic value in gastric cancer and examined the effects of caudatin on the expression of β-catenin in human gastric carcinoma cell lines. Here, we showed that caudatin treatment resulted in a dose- and time‑dependent inhibition of proliferation of the gastric carcinoma cell lines. Cell cycle analysis demonstrated that caudatin induced G0/G1 arrest and downregulated CDK2 levels. In contrast, the expression of the p21 protein was increased. AGS cells treated with caudatin exhibited typical characteristics of apoptosis, which were accompanied by activation of caspase‑3, ‑8, ‑9 and PARP. Western blot analysis and immunocytochemical staining showed that caudatin induced a reduction in β‑catenin expression and this reduction was due to proteosome-mediated degradation. This reduction in β‑catenin activation was due to the downregulation of its downstream targets cyclinD1 and c‑MYC in all gastric carcinoma cell lines. Furthermore, we demonstrated that gastric adenocarcinoma tissues and AGS cells exhibited abnormal expression of miR‑372. Additionally, caudatin downregulated the expression of oncomir miR‑372 and miR‑21, and upregulated tumor suppressor let‑7a miRNA expression. These data revealed that inhibition of Wnt/β‑catenin signaling is a novel mechanism of action for caudatin during therapeutic intervention in gastric cancers.
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, PR China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zhang
authors.forename: Xizhi
authors.initials: X
authors.lastname: Liu
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Tan
authors.forename: Celi
authors.initials: C
authors.lastname: Yang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ding
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.forename: Jianlin
authors.initials: J
authors.lastname: Zhou
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Xiang
authors.forename: Chang
authors.initials: C
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013256:Steroids / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D006027:Glycosides; D035683:MicroRNAs; D013256:Steroids; D051153:Wnt Proteins; D051176:beta Catenin; C570806:caudatin; D046988:Proteasome Endopeptidase Complex