The theoretical basis for eating peanuts to fight cancer is here! Chinese scholars discovered for the first time a new mechanism of OPC-B2 in peanut red skin against liver cancer

Liver cancer is one of the common malignant tumors in clinic, and its morbidity and mortality are ranked sixth and fourth among all cancers in the world respectively. In our country, new cases of liver cancer account for more than half of the world's total, and the mortality rate is second only to lung cancer and gastric cancer. Although there are many kinds of drugs used in the treatment of liver cancer, the problem of drug resistance often causes the failure of chemotherapy. Therefore, in-depth research on the pathogenesis of liver cancer and development of safe and effective drugs are very important for clinical diagnosis and treatment.

On August 25, 2020, Yin Huiyong's research group at the Key Laboratory of Nutrition, Metabolism and Food Safety of the Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, published an online title in the international renowned academic journal Redox Biology: [ Polyphenolic Proanthocyanidin-B2 Suppresses Proliferation of Liver Cancer Cells and Hepatocellular Carcinogenesis through Directly Binding and Inhibiting AKT Activity. ]

This study discovered for the first time that the polyphenolic active substance proanthocyanidin-B2 (OPC-B2) extracted from peanut red skin is a new type of AKT allosteric inhibitor, and can directly bind to AKT and inhibit its phosphorylation, exerting anti-tumor activity; The study also found that Lys297 and Arg86 on the AKT protein play a key role in the binding between OPC-B2 and AKT, which can provide potential therapeutic strategies for the clinical treatment of liver cancer.

OPC-B2 is a polyphenol flavonoid compound with a special structure. It is formed by the connection of two epicatechins, and it can be extracted from foods such as peanuts red skin, apples, and grapes. Previous studies have found that proanthocyanidins have very strong antioxidant and anti-inflammatory and other biological activities: Reduce cholesterol levels and protect vascular endothelial cells from free radical damage to vascular endothelium, thereby preventing cardiovascular diseases; Lower blood lipids and blood sugar, and exert anti-tumor effects, etc.

This study found that OPC-B2 extracted from peanut red skin directly binds and inhibits AKT activity and downstream signaling pathways, thereby inhibiting the proliferation, metabolism and tumor growth of liver cancer cells.

Further research found that, similar to the known AKT allosteric inhibitor MK-2206, OPC-B2 can bind to the catalytic domain and PH domain of AKT, thereby inhibiting AKT activity. In addition, Lys297 and Arg86 are the key sites for the binding of AKT to OPC-B2, and the mutation relieves the anti-tumor effect of OPC-B2.

This study showed for the first time that OPC-B2 is a new type of AKT allosteric inhibitor with significant anti-tumor efficacy.

It is reported that this work was completed by Yin Huiyong's research group from Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences and Wang Qiang's research group from Institute of Agricultural Products Processing, Chinese Academy of Agricultural Sciences. Liu Guijun, a PhD student at the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, and Associate Researcher Shi Aimin, Institute of Agricultural Products Processing, Chinese Academy of Agricultural Sciences, are the co-first authors of the paper. Researcher Yin Huiyong, Assistant Researcher Tao Yongzhen, and Researcher Wang Qiang from the Institute of Agricultural Products Processing, Chinese Academy of Agricultural Sciences are the co-corresponding authors. This work was funded by the National Key Research and Development Program of the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Chinese Academy of Sciences.