Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

Abstract

Green tea, the fresh leaves of Camellia sinensis, is not only a health-promoting beverage but also a traditional Chinese medicine used for prevention or treatment of cancer, such as lung cancer. Theabrownin (TB) is the main fraction responsible for the medicinal effects of green tea, but whether it possesses anti-cancer effect is unknown yet. This study aimed to determine the in vitro and in vivo anti-lung cancer effect of TB and explore the underlying molecular mechanism, by using A549 cell line and Lewis lung carcinoma-bearing mice. In cellular experiment, MTT assay was performed to evaluate the inhibitory effect and IC50 values of TB, and flow cytometry was conducted to analyze the cell cycle progression affected by TB. In animal experiment, mice body mass, tumor incidence, tumor size and tumor weight were measured, and histopathological analysis on tumor was performed with Transferase dUTP nick-end labeling staining. Real time PCR and western blot assays were adopted to detect the expression of C-MYC associated genes and proteins for mechanism clarification. TB was found to inhibit A549 cell viability in a dose- and time-dependent manner and block A549 cell cycle at G0/G1 phase. Down-regulation of c-myc, cyclin A, cyclin D, cdk2, cdk4, proliferation of cell nuclear antigen and up-regulation of p21, p27, and phosphate and tension homolog in both gene and protein levels were observed with TB treatment. A c-myc-related mechanism was thereby proposed, since c-myc could transcriptionally regulate all other genes in its downstream region for G1/S transitions of cell cycle and proliferation of cancer cells. This is the first report regarding the anti-NSCLC effect and the underlying mechanism of TB on cell cycle progression and proliferation of A549 cells. The in vivo data verified the in vitro result that TB could significantly inhibit the lung cancer growth in mice and induce apoptosis on tumors in a dose-dependent manner. It provides a promising candidate of natural products for lung cancer therapy and new development of anti-cancer agent.

Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway

“…Apart from polyphenols, TB attracts increasing attention in recent years due to its bioactivities and therapeutic potential . In our previous studies, TB exerted strong pro‐apoptotic effects against non‐small cell lung cancer via the p53 signalling pathway . Using xenograft model and osteosarcoma cells, this study investigated the anti‐OS effects and molecular mechanism of TB.…”

“…Viabilities of TB‐treated cells (U2OS, SAOS‐2, HOS, MG63, BMSC) was determined by MTT assay as described in our previous report . Cells were seeded on 96‐well plates with density of 1 × 10 4 cells/well in 200 μL medium for 24 hours and then treated with TB at different concentrations (0, 10, 20, 30, 40, 50, 60, 80 μg/mL) for 24 and 48 hours.…”

“…TB comprises of a family of macromolecules transformed from polyphenols, and is considered superior to TF or TR in physicochemical and medicinal properties. Previously, we reported that TB possessed strong pro‐apoptotic and cell cycle arresting effects on human carcinoma cells, making it a promising candidate for cancer therapy . To determine its anti‐OS effect, this study employed U2OS cells and performed in vivo and in vitro assays.…”

The Effects of Camellia sinensis Extract on Proliferation, Apoptosis and Oxidative Stress in Insulinoma INS-1 Cells

“…Oxidative damage can be cured with phytochemicals found in tea in diseases such as cancer (15,22). Healing properties of C. sinensis have been investigated in many types of cancers such as metastatic breast (6), human ovarian 7, lung (23), and prostate cancers (8). The effects of C. sinensis were investigated in pancreatic carcinoma cells (9,24).…”

Structural Characteristics and Hypolipidemic Activity of Theabrownins from Dark Tea Fermented by Single Species Eurotium cristatum PW-1

“…In the past few years, studies have provided important information on the functions and bioactivities of theabrownins, demonstrating that they can inhibit the activity of α-glucosidase in vitro, decrease blood glucose levels and increase glucose tolerance in mice under hyperglycemic stress [7]. Additionally, they exhibit anti-osteoporotic [8], anti-tumor [9][10][11], and hypolipidemic effects in vitro and in vivo [12][13][14][15]. Nonetheless, because of its complexity, the physicochemical properties of theabrownins are rarely studied.…”