Induction of apoptosis in human bladder cancer cells by green tea catechins

Abstract

Cell culture and animal studies have demonstrated strong chemopreventative effects of green tea and its associated polyphenols in multiple cancers, though the exact mechanisms of action are not well understood. This in vitro study examined the antiproliferative/pro-apoptotic potential of green tea extract (GTE), polyphenon-60 (PP-60), (−)-epicatechin gallate (ECG) and (−)-epigallocatechin-3-gallate (EGCG) in both normal and malignant human bladder cells. Cell growth (proliferation/ apoptosis) was measured in UROtsa (normal), SW780 (tumorigenic; low-grade), and TCCSUP (tumorigenic; high-grade) human bladder urothelial cells by cell proliferation (XTT) assay after treatment with 0-80 μg/mL of GTE, PP-60, ECG and EGCG for 72 h. Molecular signaling pathways of catechin-induced apoptosis were analyzed using Human signal transduction RT 2 Profiler PCR array (SuperArray). Compared to control-treated cells, treatment with catechin agents significantly suppressed cell growth in a dose-dependent fashion (P < 0.01), with strongest effects evoked by ECG and EGCG in UROtsa cells, ECG in low-grade RT4 and SW780 cells, and PP-60 and EGCG in high-grade TCCSUP and T24 cells. Microarray analysis indicated distinct differences in mRNA gene expression regarding growth signaling pathway activation induced by EGCG in normal/tumorigenic human bladder cell lines, providing a rationale for the putative therapeutic usage of green tea polyphenols against bladder disease.

The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals

“…Further studies are needed to establish the relationship between EGCG and PI3K/Akt/mTOR pathway and to determine whether mTOR mediates the effects of EGCG in treating brain, prostate, cervical and bladder cancers (Hsieh and Wu, 2009;Philips et al, 2009;Qiao et al, 2009;Das et al, 2010). However, many current clinical studies focus on using green tea extract or polyphenon E in a wide range of cancers such as breast cancer, leukemia, multiple myeloma and head and neck lesions (Table 1).…”

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

“…Certain phytochemicals are particularly eligible for the single compound type modality inasmuch as they are pleiotropic modulators of manifold signal transduction pathways and exhibit relatively low toxicity in non-cancerous cells (Khan et al, 2008;Lee et al, 2011b). Unfortunately, the currently Food and Drug Administration (FDA)-approved chemotherapeutic phytochemicals such as paclitaxel, docetaxel, vinblastine, and vincristine have only a singular molecular target (tubulin), whereas other phytochemical candidates such as (-)-epigallocatechin gallate and delphinidin have multiple molecular targets (Ermakova et al, 2006;Li et al, 2007;He et al, 2008;Kang et al, 2008;Shim et al, 2008Shim et al, , 2010Hwang et al, 2009;Ozbay and Nahta, 2011) and in vitro cytostatic/cytotoxic potency (Bin Hafeez et al, 2008;Hsieh and Wu, 2009;Philips et al, 2009;Qiao et al, 2009;Yun et al, 2009;Cvorovic et al, 2010;Das et al, 2010) but lack an advanced clinical development trajectory and regulatory approval status.…”

Bladder cancer prevention

“…The apoptotic process in this case is thought to involve the activation of a caspase cascade regulated by proteins from the BcL-2 family [46]. A study on human bladder cancer cells also confirmed the antiproliferative properties of epigallocatechin gallate, and polyphenon 60, epicatechin gallate, and the green tea extract were shown to have similar proapoptotic effects [44].…”

“…Studies conducted on cell lines and animal models have demonstrated the strong chemoprotective properties associated with its high polyphenol content [43,44]. The link between green tea and the reduced risk of many cancers is common knowledge, and successive studies have confirmed its beneficial properties.…”