title: Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism.
abstract: Green tea, the fresh leaves ofCamellia 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 thein vitroandin vivoanti-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 ofC-MYCassociated 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. Thein vivodata verified thein vitroresult 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.
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences Inc. Hangzhou, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Wangdong
authors.initials: W
authors.lastname: Jin
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Yingfei
authors.initials: Y
authors.lastname: He
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Weiji
authors.initials: W
authors.lastname: Yang
authors.affiliation: Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences Inc. Hangzhou, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Du
authors.affiliation: Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences Inc. Hangzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences Inc. Hangzhou, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Guo
authors.affiliation: The Second Clinical Medical College, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Hangzhou First People's Hospital Hangzhou, China.
authors.forename: Xiaoqiao
authors.initials: X
authors.lastname: Dong
authors.affiliation: Hangzhou First People's Hospital Hangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Yu
authors.affiliation: Theabio Co., Ltd Hangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Luwei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical University Hangzhou, China.
authors.forename: Peijian
authors.initials: P
authors.lastname: Tong
authors.affiliation: Institute of Orthopaedics and Traumatology, Zhejiang Chinese Medical UniversityHangzhou, China; Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences Inc.Hangzhou, China.
authors.forename: Letian
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
keywords: TUNEL; c-myc; cell cycle; lung cancer; theabrownin