br Cancer prevention and anti tumor effects

Cancer prevention and anti-tumor effects of black tea Cancer is the most common cause of human mortality worldwide. Cancer cells are capable of limitless replication potential due to their self-sufficient growth signals and their resistant to anti-growth signals from host defense that enable them to evade apoptosis. Furthermore, they can sustain angiogenesis that can lead to tissue invasion and metastasis [2]. Targeting the regulation of key molecules and cellular signaling pathways in tumorigenesis by natural products was effective in preventing or reducing risk of cancer [3]. There are many reports on the efficacy of the anti-tumor and cancer prevention activity of black tea. For instance, studies from Baker et al. [4] and Doral et al. [5] support the cancer chemo-preventive effect of black tea in the development of prostate cancer, ovarian cancer and rectal cancer. However, others [6,7] do not. The discrepancy of the effects could be a result of actual dosage differences among studies with unspecified amount ingestion of bioactive tea polyphenols. Daily consumption of black tea in women lowered the concentration of 17β-estradiol (E2), which may reduce hormone-related cancer risk [8] (Table 3). Regular black tea consumption is also associated with the reduced risk of ovarian and Senexin B cancer in female subjects [9–11]. Furthermore, several research groups have attempted to elucidate the molecular mechanisms of black tea and its polyphenols. Drinking black tea reduced incidence and number of skin papilloma in 7,12-dimethylbenz[a]anthracene (DMBA)-treated mice through activation of detoxification enzymes and decreased lipid peroxidation [12]. Oral administration of black tea polyphenols delayed tumorigenesis, reduced tumor number and volume in DMBA-induced mouse skin carcinogenesis through induction of apoptosis in tumor cells [13]. Topical application of combined black tea polyphenols and resveratrol synergistically inhibited DMBA/TPA-induced skin carcinogenesis by reducing tumor incidence, number and volume. Mechanistic study showed that this combination down-regulated mitogen-activated protein kinases (MAPKs) and increased tumor suppressor gene p53 and apoptosis [14]. Consistent with the results in skin cancer model, oral intake of black tea polyphenols or extract also suppressed DMBA-induced mammary tumors and oral tumors by scavenging reactive oxygen species (ROS) that reduced the oxidative stress [15] and down-regulating cyclyoxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB) and protein kinase B (Akt) [15], and interfering with the activity of carcinogen metabolizing enzymes [16]. In DMH (1,2-dimethylhydrazine)-induced colorectal tumor model, consumption of tea with high content polymeric black tea polyphenols inhibited the tumorigenesis via down-regulation of Wnt/β-catenin pathway and proliferative gene expression [17]. Oral administration of black tea polyphenols was also effective against arsenic-induced formation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) through up-regulation of DNA repair enzymes in Swiss albino mice [18]. One common feature in the effects of black tea in antagonizing various chemical-induced carcinogenesis is the activation of the detoxification enzymes. The detoxifying enzyme system plays an important role in determining the final fate of carcinogens/procarcinogens and their subsequent impact on carcinogenesis [19]. Regulation of many detoxifying enzymes is mediated by the transcription factor nuclear factor E2-related factor 2 (Nrf2) that binds to the antioxidant response element (ARE)/electrophile response element (EpRE), which is located in the promoter region of related genes to initiate gene expression. Ingredients in black tea including EGCG activate Nrf2 and up-regulate the protective enzymes [19,20]. In addition to Nrf2 activation, there are many other important mechanisms that contribute to the anti-carcinogenic effects by black tea polyphenols.