Tea polyphenols induce S phase arrest and apoptosis in gallbladder cancer cells

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer.

[1]  X. Liang,et al.  EIF3D promotes gallbladder cancer development by stabilizing GRK2 kinase and activating PI3K-AKT signaling pathway , 2017, Cell Death & Disease.

[2]  Yijian Zhang,et al.  Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer , 2017, Journal of Experimental & Clinical Cancer Research.

[3]  Weiren Huang,et al.  EGCG inhibited bladder cancer SW780 cell proliferation and migration both in vitro and in vivo via down-regulation of NF-κB and MMP-9. , 2017, The Journal of nutritional biochemistry.

[4]  S. Ou,et al.  Green tea polyphenols induce cell death in breast cancer MCF-7 cells through induction of cell cycle arrest and mitochondrial-mediated apoptosis , 2017, Journal of Zhejiang University-SCIENCE B.

[5]  Shuai Zhao,et al.  Prohibitin overexpression predicts poor prognosis and promotes cell proliferation and invasion through ERK pathway activation in gallbladder cancer , 2016, Journal of experimental & clinical cancer research : CR.

[6]  W. Lu,et al.  20(S)-ginsenoside Rg3 promotes senescence and apoptosis in gallbladder cancer cells via the p53 pathway , 2015, Drug design, development and therapy.

[7]  S. Anand,et al.  Isolation of Primary Human Colon Tumor Cells from Surgical Tissues and Culturing Them Directly on Soft Elastic Substrates for Traction Cytometry. , 2015, Journal of visualized experiments : JoVE.

[8]  Yang Cao,et al.  Fibronectin promotes cell proliferation and invasion through mTOR signaling pathway activation in gallbladder cancer. , 2015, Cancer letters.

[9]  W. Lu,et al.  Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway , 2014, Nature Genetics.

[10]  Lu Li,et al.  Piperine induces apoptosis of lung cancer A549 cells via p53-dependent mitochondrial signaling pathway , 2014, Tumor Biology.

[11]  Q. Hu,et al.  Cytotoxicity and apoptotic effects of tea polyphenol-loaded chitosan nanoparticles on human hepatoma HepG2 cells. , 2014, Materials science & engineering. C, Materials for biological applications.

[12]  B. Liu,et al.  A Novel Regulatory Mechanism of Pim-3 Kinase Stability and Its Involvement in Pancreatic Cancer Progression , 2013, Molecular Cancer Research.

[13]  H. Weng,et al.  Prognostic significance of nemo-like kinase (NLK) expression in patients with gallbladder cancer , 2013, Tumor Biology.

[14]  M. Jackson,et al.  Green Tea Polyphenols Induce p53-Dependent and p53-Independent Apoptosis in Prostate Cancer Cells through Two Distinct Mechanisms , 2012, PloS one.

[15]  L. Soane,et al.  A New View of the Lethal Apoptotic Pore , 2012, PLoS biology.

[16]  A. Gomes,et al.  Black tea polyphenols induce human leukemic cell cycle arrest by inhibiting Akt signaling , 2012, The FEBS journal.

[17]  Thoria Donia,et al.  Growth inhibition of human non-small lung cancer cells h460 by green tea and ginger polyphenols. , 2012, Anti-cancer agents in medicinal chemistry.

[18]  U. Dutta.  Gallbladder cancer: Can newer insights improve the outcome? , 2012, Journal of gastroenterology and hepatology.

[19]  S. Shankar,et al.  Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. , 2011, Biochemical pharmacology.

[20]  Y. Tokuda,et al.  Enhancement of phagocytic activity of macrophage-like cells by pyrogallol-type green tea polyphenols through caspase signaling pathways , 2010, Cytotechnology.

[21]  J. Donohue,et al.  Adjuvant therapy for gallbladder carcinoma: the Mayo Clinic Experience. , 2009, International journal of radiation oncology, biology, physics.

[22]  Jen-kun Lin.  Cancer Chemoprevention by Tea Polyphenols Through Modulating Signal Transduction Pathways , 2002, Archives of pharmacal research.

[23]  R. Rodrigo,et al.  Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases. , 2016, Current medicinal chemistry.

[24]  T. Chan,et al.  Recent advances on tea polyphenols. , 2012, Frontiers in bioscience.