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

Abstract

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.

Targeting NF-κB signaling pathway in cancer by dietary polyphenols

“…EGCG and theaflavins induce apoptosis in human cervical cancer cells by suppressing the activation of NF-jB and Akt via blocking phosphorylation of jBa and jBb subunits, thus down-regulating COX-2 (Singh et al 2011). Other molecular mechanisms of apoptosis induction by tea polyphenols include upregulating the expression levels of p53, p21, p73, caspase-3, caspase-9, caspase-8, and Bax; while down-regulating the expression levels of Bcl-2 and Bcl-xL (Zhao et al 2014;Wang et al 2018). Synergistic anticancer effects of bleomycin and tea polyphenols in human cervical cancer cells via induction of apoptotic pathways were studied, and it was suggested that both of these agents might provide an effective combination therapy for cervical cancer (Alshatwi et al 2016).…”

Anticancer Effects of Green Tea and the Underlying Molecular Mechanisms in Bladder Cancer

“…Various cancer-related molecules have been reported to be modulated by GTPs. In fact, many studies have reported that GTPs inhibited cell growth and induced apoptosis in various types of malignancies [ 19 , 27 , 28 ]. In addition, these polyphenols modulate the functions of various cancer-related signaling molecules.…”

“…In general, GTPs are considered to be safe because they are natural compounds. GTPs were found to have no toxic effects on normal cells in the gallbladder [ 28 ]. Furthermore, 24-h treatment with 20 μg/mL and 40 μg/mL of EGCG increased the frequency of apoptotic cells in colon cancer cell lines (COLO205), while no significant changes were observed in normal colon epithelial cells (NCM460) [ 19 ].…”

Pharmacological Properties of Polyphenols: Bioavailability, Mechanisms of Action, and Biological Effects in In Vitro Studies, Animal Models, and Humans

“…Many interesting findings have also been published regarding the protective benefits of polyphenols against cancer. Studies have shown how treatment with 140 µM tea polyphenols induces mitochondrial-mediated apoptosis by activating the caspase-3 and PARP apoptotic cascade in human gallbladder cancer cells [53], 0.5-5 µg/mL of EGCG reduces the cell viability and increases the apoptosis rate of myeloid-derived suppressor cells, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway [54], and 15 µM EGCG inhibits Excision Repair Cross-Complementation Group1/Xeroderma Pigmentosum group F, thereby inhibiting DNA repair and enhancing cisplatin sensitivity in human lung cancer cells [55]. A total of 0.1-1 mM catechin with lysine has also been proven to have antimigratory effects in breast, pancreatic, and colorectal cell lines through JAK2/STAT3 and Wnt pathway inhibition [56].…”