Ellagic Acid Exert Anti-non-small Cell Lung Cancer Activity In Vitro And In Vivo

Diet has a very important role in disease,and many studies have confirmed that dietary factors have a positive impact on the risk of cancer,especially the intake of fruits and vegetables,which is closely related to the occurrence of cancer.Therefore,exploring the preventive or therapeutic effects of fruits and vegetables or processed foods on diseases and clarifying its mechanism is of great significance to food nutrition and health.Wine is rich in polyphenols,such as resveratrol has a chemical preventive and therapeutic effect,through the targeting of cancer-driven molecules against many types of cancer.Among them,ellagic acid is also a polyphenol substance commonly found in wine and has a series of biological activities.However,its efficacy and molecular mechanism in lung cancer are not completely elucidated.This study tested the anti-lung cancer activity of 11 wine components and reported that a natural polyphenol compound ellagic acid(EA)inhibited lung cancer cell proliferation at an efficacy approximately equal to that of resveratrol.EA inhibited lung cancer cell proliferation in a time-and dose-dependent manner,and EA significantly increased the expression of the autophagosomal marker LC3-?,as well as inactivation of the mechanistic target of mTOR signaling pathway.In this process,the cancerous inhibitor of protein phosphatase 2A(CIP2A)plays an important role.Mechanistically,EA elevated autophagy-associated cell death by down-regulating the expression of CIP2A.CIP2A overexpression attenuated EA-induced autophagy of lung cancer cells,whereas CIP2A knockdown enhanced EA-induced autophagy of lung cancer cells.In vivo animal models further demonstrated the inhibitory effect of EA on lung cancer.Treatment of tumor-bearing mice with different doses of EA for 24 days showed that EA could significantly inhibit tumor growth with no obvious side effects.By detecting tumor tissue protein,the results showed that EA can also suppression of CIP2A levels and increased autophagy.In addition,EA potentiated the inhibitory effects of the natural compound celastrol on lung cancer cells in vitro and in vivo by enhancing autophagy and downregulating CIP2A.These findings indicate that EA may be a promising chemotherapeutic agent for lung cancer,and that the combination of EA and celastrol may have applicability for the treatment of this disease,and provide theoretical support for the study of anticancer efficacy of polyphenol.