Tea and Citrus maxima complex induces apoptosis of human liver cancer cells via PI3K/AKT/mTOR pathway in vitro

OBJECTIVE: In this study, black tea and Citrus maxima (BT-CM), yellow tea and C. maxima (YT-CM), green tea and C. maxima (GT-CM) as subjects, the active ingredient content and antioxidant activity of three tea and C. maxima (T-CM) were analyzed. The effects of three T-CMs on apoptosis of liver cells in vitro and its mechanism were further explored. METHODS: National standard method and HPLC were used for active ingredient analysis. MTT, cell flow cytometry and Western blot were used to analyze the effects of three T-CMs on cell proliferation, apoptosis, and its underlying molecular mechanism. RESULTS: The content of tea polyphenols, free amino acids, ratio of polyphenols and amino acids, ester catechins, non-ester catechins and caffeine in YT-CM and GT-CM was significantly higher than that of BT-CM. The in vitro antioxidant capacity of YT-CM and GT-CM was also significantly stronger than that of BT-CM. Three T-CMs had the effects of inhibiting proliferation, arresting cell cycle and inducing apoptosis in HepG2 and Bel7402 cells, especially YT-CM and GT-CM. Western blot analysis showed three T-CMs activated PI3K/AKT/mTOR signaling pathway and regulated the expression levels of apoptosis-related proteins Bax, Bcl-2 and Caspase-3/9. YT-CM and GT-CM had better ability to change the signal pathway than BT-CM. CONCLUSION: In short, T-CMs, which combined different degrees of fermentation tea with C. maxima, were rich in nutrients and biologically active substances. T-CMs, especially YT-CM and GT-CM, are healthy drinks that help to prevent and treat liver cancer.