Green tea catechin extract in intervention of chronic breast cell carcinogenesis induced by environmental carcinogens

Abstract

Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically-achievable concentration of 2.5μg/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.

Role of Green Tea in Reducing Epidermal Thickness upon Ultraviolet Light-B Injury in BALB/c Mice

“…Green tea is a dietary plant that contains an important source of polyphenols and next to water, it is the second most commonly consumed beverage in the world after black tea, produced mainly from a single plant species Camellia sinensis [13][14][15]. Green tea has potential beneficial effects such as solar ultraviolet protection, antimutagenic, antidiabetic, antiinflammatory, anticancer, antioxidant, and immunomodulatory effects.…”

Chronic Exposure to Combined Carcinogens Enhances Breast Cell Carcinogenesis with Mesenchymal and Stem-Like Cell Properties

“…In our previous reports, we demonstrated that GTCs, at non-cytotoxic levels, were capable of suppressing breast cell carcinogenesis induced by NB or PhIP [33]–[35]. EGCG, the major catechin present in green tea extract, is the most commonly studied preventive GTC [44], but some studies have shown that ECG may be more effective than EGCG in intervention of carcinogenesis [34], [45], [46].…”

Therapeutic properties of green tea against environmental insults

“…Cellular studies have shown that EGCG and GTE protect against smoke-induced cellular proliferation [62, 71, 77], DNA damage [66, 80, 83], oxidative stress [22, 62, 71], and tumorigenesis [56, 71] through cell signaling pathways [71, 77]. More specifically, Syed et al reported that EGCG pretreatment (20–80 μM) of normal human bronchial epithelial cells (NHBE) resulted in significant inhibition of cigarette smoke condensate (CSC)-induced cell proliferation [77].…”

“…Aside from inhibiting smoke-induced cellular proliferation in normal cells, green tea polyphenols, such as GTP, EGCG, ECG, EGC, and EC, also reduced smoke-induced DNA damage [66, 71, 80]. Pretreatment with 20–100μg/mL GTP for 2 h resulted in a dose-dependent decrease in smoke-mediated DNA damage in A549 cells, and GTP concentration was inversely correlated with the extent of DNA damage observed [66].…”