title: Anti-Warburg effect of rosmarinic acid via miR-155 in gastric cancer cells.
abstract: BACKGROUND
  The Warburg effect refers to glycolytic production of adenosine triphosphate under aerobic conditions, and is a universal property of most cancer cells. Chronic inflammation is a key factor promoting the Warburg effect. This study aimed to determine whether rosmarinic acid (RA) has an anti-Warburg effect in gastric carcinoma in vitro and in vivo. The mechanism for the anti-Warburg effect was also investigated.
  
  
  METHODS
  An MTT assay was used to examine MKN45 cell growth in vitro. An enzyme-linked immunosorbent assay was used to detect proinflammatory cytokines. Real-time polymerase chain reaction was used to evaluate levels of microRNA expression in cells. Protein expression was determined by Western blotting assay. Mouse xenograft models were established using MKN45 cells to assess the anti-Warburg effect in gastric carcinoma in vivo.
  
  
  RESULTS
  RA suppressed glucose uptake and lactate production. It also inhibited expression of transcription factor hypoxia-inducible factor-1α, which affects the glycolytic pathway. Inflammation promoted the Warburg effect in cancer cells. As expected, RA inhibited proinflammatory cytokines and microRNAs related to inflammation, suggesting that RA may suppress the Warburg effect via an inflammatory pathway, such as that involving interleukin (IL)-6/signal transducer and activator of transcription-3 (STAT3). miR-155 was found to be an important mediator in the relationship between inflammation and tumorigenesis. We further showed that miR-155 was the target gene regulating the Warburg effect via inactivation of the IL-6/STAT3 pathway. Moreover, we found that RA suppressed the Warburg effect in vivo.
  
  
  CONCLUSIONS
  RA might potentially be a therapeutic agent for suppressing the Warburg effect in gastric carcinoma.
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Zhai
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Dongyue
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Pusheng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D000097123:Rosmarinic Acid
chemical_list: D000255:Adenosine Triphosphate; D002934:Cinnamates; D053630:Depsides; D015850:Interleukin-6; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; D000097123:Rosmarinic Acid; C524942:MIRN155 microRNA, human
keywords: MKN45; Warburg effect; inflammation; miR-155; rosmarinic acid