Anti-Warburg effect of rosmarinic acid via miR-155 in colorectal carcinoma cells.
The Warburg effect, glycolytic production of ATP under aerobic conditions, is found to be a universal feature of most cancer cells. Our study was aimed to determine whether rosmarinic acid (RA) had the anti-Warburg effect activity against colorectal carcinoma. Furthermore, the mechanism for the anti-Warburg effect by RA would be investigated. In our study, we found that RA suppressed glucose consumption and lactate generation in colorectal carcinoma cells; meanwhile, RA inhibited the expression of transcription factor hypoxia-inducible factor-1α (HIF-1α) that affects the glycolytic pathway. Chronic inflammation is a key promoting factor of the Warburg effect. As we supposed, the present study also showed that RA could not only repress proinflammatory cytokines using enzyme-linked immunosorbent assay but it could also suppress microRNAs related to inflammation by real-time PCR. Therefore, we proposed that RA may inhibit the Warburg effect by suppressing the inflammatory response of colorectal carcinoma cells. Recent studies have provided evidence that miR-155 was an important mediator between inflammation and carcinogenesis. We further showed that miR-155 acted to repress the Warburg effect through the mechanism of inactivating the IL-6/STAT3 pathway. Above all, RA might be a potential therapeutic agent against colorectal carcinoma.
aState Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology bLaboratory of Integrative Medicine Surgery cDepartment of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou dDepartment of Clinical Pharmacy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yichun
Y
Xu
Shuai
S
Han
Kesheng
K
Lei
Xinnan
X
Chang
Ke
K
Wang
Zhou
Z
Li
Jianwen
J
Liu
D000255:Adenosine Triphosphate / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053630:Depsides / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000097123:Rosmarinic Acid
D000255:Adenosine Triphosphate; D002934:Cinnamates; D053630:Depsides; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; D000097123:Rosmarinic Acid; C524942:MIRN155 microRNA, human