Molecular Mechanisms and Therapeutic Effects of (−)-Epicatechin and Other Polyphenols in Cancer, Inflammation, Diabetes, and Neurodegeneration

Figure 2

Proposed model of the interference of (−)-epicatechin with cancer signaling, metabolism, and proliferation. (−)-Epicatechin stimulates mitochondrial respiration and biogenesis, thus interfering with Warburg metabolism. At the cell signaling level, the compound inhibits Erk signaling, which interferes with other signaling pathways including EGFR that are known to be hyperactive in cancer. (−)-Epicatechin through Erk and/or other signaling pathways leads to an activation of mitochondrial oxidative phosphorylation, which interferes with Warburg metabolism. Other targets that are inhibited by (−)-epicatechin in cancer cells are NF-κB, Akt, and histone acetyltransferases (HATs). As a result, (−)-epicatechin interferes with cancer signaling, thus rendering the cells more susceptible to apoptosis, an effect that could be utilized to sensitize cancer cells to radiation treatment or chemotherapy. It should be noted that (−)-epicatechin exerts a distinct protective response in noncancerous normal tissue (not shown). This highlights the importance not to generalize the effects but to include detailed information including cell type and treatment regimen.