Multistage carcinogenesis process as molecular targets in cancer chemoprevention by epicatechin-3-gallate.

The consumption of green tea has long been associated with a reduced risk of cancer development. (-)-Epicatechin-3-gallate (ECG) or (-)-epigallocatechin-3-gallate (EGCG) are the major antioxidative polyphenolic compounds of green tea. They have been shown to exert growth-inhibitory potential of various cancer cells in culture and antitumor activity in vivo models. ECG or EGCG could interact with various molecules like proteins, transcription factors, and enzymes, which block multiple stages of carcinogenesis via regulating intracellular signaling transduction pathways. Moreover, ECG and EGCG possess pharmacological and physiological properties including induction of phase II enzymes, mediation of anti-inflammation response, regulation of cell proliferation and apoptosis effects and prevention of tumor angiogenesis, invasion and metastasis. Numerous review articles have been focused on EGCG, however none have been focused on ECG despite many studies supporting the cancer preventive potential of ECG. To develop ECG as an anticarcinogenic agent, more clear understanding of the cell signaling pathways and the molecular targets responsible for chemopreventive and chemotherapeutic effects are needed. This review summarizes recent research on the ECG-induced cellular signal transduction events which implicate in cancer management.

Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway.

Inflammatory bowel diseases have been a risk factor of colorectal cancer (CRC). The reactive oxygen species (ROS) generated by inflammatory cells create oxidative stress and contribute to neoplastic transformation, proliferation, and even metastasis. Previously, resveratrol (RS) and pterostilbene (PS) had been reported to prevent chemical-induced colon carcinogenesis by anti-inflammatory and pro-apoptotic properties. In this study, we investigated whether RS and PS could prevent the azoxymethane (AOM)-induced colon tumorigenesis via antioxidant action and to explore possible molecular mechanisms. Male BALB/c mice were injected with AOM (5 mg/kg of body weight) with or without RS or PS, and at the end of the protocol, all of the mice were euthanized and colons were analyzed. Administrations of PS can be more effective than RS in reducing AOM-induced formation of aberrant crypt foci (ACF), lymphoid nodules (LNs), and tumors. We also find that PS is functioning more effectively than RS to reduce nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation of protein kinase C-ß2 (PKC-ß2) and decreasing downstream target gene expression, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and aldose reductase (AR) in mouse colon stimulated by AOM. Moreover, administration of RS and PS for 6 weeks significantly enhanced expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1) and glutathione reductase (GR), via activation of NF-E2-related factor 2 (Nrf2) signaling. When the above findings are taken together, they suggest that both stilbenes block cellular inflammation and oxidative stress through induction of HO-1 and GR, thereby preventing AOM-induced colon carcinogenesis. In comparison, PS was a more potent chemopreventive agent than RS for the prevention of colon cancer. This is also the first study to demonstrate that PS is a Nrf2 inducer and AR inhibitor in the AOM-treated colon carcinogenesis model.