Molecular mechanisms underlying the anticancer activities of licorice flavonoids

Licorice has been commonly used in traditional Chinese medicine for treatment of gastric, liver, and respiratory disease conditions for more than two thousand years. It is a major component of several Chinese patent medicines certificated by National Medical Products Administration that possess great anticancer activities. To comprehensively summarize the anticancer activities of licorice flavonoids, explain the underlying molecular mechanisms, and assess their therapeutic potentials and side-effects. PubMed, Research Gate, Web of Science, Google Scholar, academic journals, and Science Direct were used as information sources, with the key words of "anticancer", "licorice", "flavonoids", and their combinations, mainly from 2000 to 2019. Sixteen licorice flavonoids are found to possess anticancer activities. These flavonoids inhibit cancer cells through blocking cell cycle and regulating multiple signaling pathways. The major pathways targeted by licorice flavonoids include: the MAPK pathway, PI3K/AKT pathway, NF-κB pathway, death receptor - dependent extrinsic signaling pathway, and mitochondrial apoptotic pathway. Licorice flavonoids are a group of versatile molecules that have pleiotropic effects on cell growth, survival and cell signaling. Many of the flavonoids possess inhibitory activities toward cancer cell growth and hence have a great therapeutic potential in cancer treatment. However, additional preclinical studies are still needed to assess their in vivo efficacy and possible toxicities. It is also imperative to evaluate the effects of licorice flavonoids on the metabolism of other drugs and explore the potential synergistic mechanism.