The green tea compound, (−)‐epigallocatechin‐3‐gallate downregulates N‐cadherin and suppresses migration of bladder carcinoma cells

Abstract

Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (-)-epigallocatechin gallate (EGCG-the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC(50) range of 70-87 microM. At a concentration of 20 microM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N-cadherin in a dose-dependent manner where reduction in N-cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P </= 0.05) with no detectable toxicity. EGCG inhibited bladder carcinoma cell growth and suppressed the in vitro migration capacity of cells via downregulation of N-cadherin and inactivation of Akt signaling. Continuous administration of EGCG to mice revealed significant inhibition of tumor growth in vivo indicating a possible preventative role for green tea in bladder cancer.

Expanding therapeutic targets in bladder cancer: the PI3K/Akt/mTOR pathway

“…17 Another example is (-)-epigallocatechin gallate, a phytochemical in green tea, that has been seen to reduce T24 UCC cell proliferation and viability in a dose-and time-dependent manner thought because of inactivation of the PI3K/Akt pathway. 77,78 Perhaps, some of the more popular alternatives to mTORspecific inhibition have been in targeting PI3K and Akt. Although clinical studies evaluating the role of PI3K inhibition PI3K inhibition is comprised of both pan-PI3K inhibitors and isoform-specific inhibitors.…”

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“…Downregulation of N-cadherin has also been exhibited by (-) EGCG along with suppression of metastasis of bladder carcinoma cells. [21] Pre-clinical studies have shown that (-) EGCG is capable of inhibiting cell proliferation and inducing cellular death in a wide range of cancer cells including head and neck tumor, prostate cancer, lung cancer, mouse embryonic fibroblast cell tumor, breast cancer, human epidermoid carcinoma, human osteogenic sarcoma, laryngeal squamous carcinoma cells, renal cell carcinoma, nasopharyngeal carcinoma, intestinal tumor, gastric carcinoma, colorectal cancer, hypopharyngeal carcinoma, and pancreatic cancer cells. Various studies have reported that (-) EGCG potently induces apoptosis and arrest of cell cycle in tumor cells but not in their physiological counterparts.…”

The Role of Natural Antioxidants in Cancer Disease

“…Perhaps most notably, the anticancer properties of green tea flavanols have been reported in animal models and in human cell lines , as well as in human intervention studies [60]. On the other hand, green tea consumption has been proposed as significantly reducing the risk of cancer of the biliary tract [133], bladder [110], breast [74], and colon [72]. Many of the anti-cancer properties associated with green tea are thought to be mediated by the flavanol Epigallocatechin gallate (EGCG), which has been shown to induce apoptosis and inhibit cancer cell growth by altering the expression of cell cycle regulatory proteins and the activity of signaling proteins involved in cell proliferation, transformation, and metastasis [66].…”