title: Omega-3 PUFAs induce apoptosis of gastric cancer cells via ADORA1.
abstract: Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been suggested to have anti-cancer effects by epidemiological and clinical studies. However, their underlying anti-cancer mechanisms are still unclear. In this study, we examined the influence of two Omega-3 PUFAs (DHA and EPA) on the proliferation and apoptosis of gastric cancer (GC) cells, and found that DHA and EPA reduced the viability of GC cells and induced apoptosis by activating caspase-3. Moreover, we screened the expression profile of apoptosis-related genes in GC cells upon the treatment of DHA and/or EPA, and discovered that ADORA1, one subtype of adenosine receptor functionally involved in cell death, was up-regulated in response to DHA and EPA. Importantly, when GC cells were treated with a selective ADORA1 antagonist, DPCPX, the DHA/EPA-induced apoptosis was substantially reduced. Taken together, our results suggest that the anti-cancer effect of Omega-3 PUFAs on gastric cancer is at least partly dependent on activating the ADORA1-mediated apoptosis pathway.
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Binya
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Cao
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D043682:Receptor, Adenosine A1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D015525:Fatty Acids, Omega-3; D043682:Receptor, Adenosine A1; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid