Theabrownins Produced via Chemical Oxidation of Tea Polyphenols Inhibit Human Lung Cancer Cells in vivo and in vitro by Suppressing the PI3K/AKT/mTOR Pathway Activation and Promoting Autophagy

Abstract

During the fermentation of dark tea, theabrownins (TBs), carbohydrates, and other substances get irreversibly complex. Recent research on the biological activity of TBs is not based on free TBs. In the present study, some brown polyphenol oxidized polymers, the generalized TBs (TBs-C), were prepared via alkali oxidation from tea polyphenols (TP). We also investigated the inhibitory mechanism of TBs-C on non-small-cell-lung cancer (NSCLC). TBs-C demonstrated a stronger inhibition than TP on the NSCLC cell lines A549, H2030, HCC827, H1975, and PC9. Next, A549 and H2030 cell lines were selected as subjects to explore this mechanism. TBs-C was found to inhibit proliferation, promote apoptosis, and induce G1 cell-cycle arrest in the cells. In addition, TBs-C increased autophagic flux, which in turn promoted the death of lung cancer cells. Moreover, TBs-C suppressed the PI3K/AKT/mTOR pathway activation, promoted autophagy, and increased the expression of p21 downstream of AKT, which resulted in G1 cell-cycle arrest. In xenotransplanted NSCLC nude mice derived from A549 cells, TBs-C could significantly suppress tumor growth by inhibiting the PI3K/AKT/mTOR pathway without causing hepatotoxicity, brain toxicity, or nephrotoxicity. We believe that our present findings would facilitate advancement in the research and industrialization of TBs.