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.
Highlights
IntroductionLung cancer has the highest incidence rate of cancer and becomes the leading cause of cancer death (about 1.38 million deaths annually) in the world (Siegel et al, 2015; Torre et al, 2015)
Lung cancer has the highest incidence rate of cancer and becomes the leading cause of cancer death in the world (Siegel et al, 2015; Torre et al, 2015)
Roswell Park Memorial Institute (RPMI) 1640 medium, fetal bovine serum (FBS), and 0.25% trypsin were obtained from Gibco BRL (Grand Island, NY, USA). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dimethyl sulfoxide (DMSO) were obtained from Sigma
Summary
Lung cancer has the highest incidence rate of cancer and becomes the leading cause of cancer death (about 1.38 million deaths annually) in the world (Siegel et al, 2015; Torre et al, 2015). Kuntze (Theaceae), is the most ancient healthpromoting beverage in the world It has been officially described as a medicine by the earliest national pharmacopeia ‘Xin Xiu Ben Cao’ (Newly Revised Materia Medica, AD 659) in Tang Dynasty of China, and was characterized with bitter and sweet flavor as well as cold and non-toxic nature, which can function to eliminate the heat, phlegm, and toxins from body. In view of the TB’s key role in green tea, it can be expected that TB has a certain anti-lung cancer potential representative for the same activity of green tea.
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