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Anti-Warburg effect of rosmarinic acid via miR-155 in colorectal carcinoma cells

Xu, Yichun; Han, Shuai; Lei, Kesheng; Chang, Xinnan; Wang, Ke; Li, Zhou; Liu, Jianwen

European Journal of Cancer Prevention: November 2016 - Volume 25 - Issue 6 - p 481–489
doi: 10.1097/CEJ.0000000000000205
Research Papers: Gastrointestinal Cancer
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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

* Ke Wang, Zhou Li, and Jianwen Liu contributed equally to this article.

Correspondence to Jianwen Liu, BSc, MSc, State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China Tel: +86 21 6425 2044; fax: +86 21 6425 2044; e-mail: liujian@ecust.edu.cn

Received February 9, 2015

Accepted July 29, 2015

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