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

Abstract

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.