Inhibitory effects of tea polyphenols by targeting cyclooxygenase-2 through regulation of nuclear factor kappa B, Akt and p53 in rat mammary tumors

Abstract

Breast cancer has become the second leading cause of cancer-related deaths worldwide. The control of this disease can be achieved through chemoprevention, which refers to the consumption of synthetic or naturally occurring agents to block, reverse, or delay the process of tumor development. Tea (Camellia sinensis), the most widely consumed beverage, has shown promises in the field of cancer chemoprevention. Inhibition of tumorigenesis by green or black tea polyphenols has been demonstrated in various in vitro and in vivo models. Here, we examined the inhibitory effect of green tea polyphenol (GTP) and black tea polyphenol (BTP) on the development of mammary tumors-induced by 7, 12-dimethylbenz (a) anthracene (DMBA) in female, Wistar rats. 13% and 33% of animals developed tumors in GTP and BTP supplemented groups, respectively. Both GTP and BTP are effective in significantly inhibiting the cumulative number of mammary tumors (by~92% and 77%, respectively) and in reducing their growth. Mechanistically, we investigated the effects of GTP and BTP on the components of cell signaling pathways, connecting biomolecules involved in cancer development. GTP and BTP supplementation as a sole source of drinking solution leads to scavenging of reactive oxygen species (ROS) (by~72% and 69%, respectively) by inhibiting cyclooxygenase-2 (Cox-2) and inactivation of phosphorylated forms of nuclear factorkappa B (NF-kB) and Akt. Altogether, the study suggests that both cultivars of tea, i.e. green and black, have antitumorigenic potential against DMBA-induced mammary tumorigenesis in Wistar rats. Further studies such as large and long term cohort studies and clinical trials are warranted.

Dysregulation of the NF-κB pathway as a potential inducer of bipolar disorder

“…These isoforms act as homodimers and were shown to form heterodimers in mice (Yu et al 2006). Since COX-2 is regulated by NF-κB, it became the target of anti-COX therapeutics (Lee et al 2004, Roy et al 2011, although the use of COX-2 inhibitors in BD is currently not recommended because its potential interactions with lithium may have severe side effects. Preliminary observations of COX-1 inhibitors, however, suggest beneficial effects on the depressive symptoms of bipolar patients (Fond et al 2013).…”

Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage

“…9,10 Previous reports from the authors' lab have shown the chemopreventive potential of tea polyphenols in both in vivo and in vitro conditions. 11,12 Chemoprevention through the use of naturally occurring phytochemicals has emerged as a successful strategy for cancer prevention and treatment. 13 But one major drawback associated with these phytochemicals is their inefficient systemic delivery and bioavailability under in vivo conditions; hence, the applicability of chemoprevention to humans has met with limited success.…”

Paradoxical Effect of Nonalcoholic Red Wine Polyphenol Extract, Provinols™, in the Regulation of Cyclooxygenases in Vessels from Zucker Fatty Rats (fa/fa)

“…Consistent with our findings, a previous study from Kane et al [40] showed that red wine polyphenols reduced angiotensin II-induced COX-2 overexpression in rat vessels. Previous publications have also reported an inhibitory effect of red wine extract and tea polyphenols on COX-2 activity [20, 38]. However, a recent study evaluated the effect of several food polyphenols, including resveratrol, a component of red wine polyphenols, on the activity of COX-2 and reported that although these compounds could elicit the inhibition of COX–2, their potency was 100- to 1000-fold lower compared to known pharmacological inhibitors of COX-2 such as celecoxib and indomethacin [41].…”

“…In the present work, we found that Provinols reduced NF- κ B in the aorta, but not in SMA, accounting potentially for reducing COX-2 expression. Previously, it has been shown that tea polyphenols inactivated phosphorylated forms of nuclear NF- κ B and reduced COX-2 expression in rat mammary tumours [38]. Furthermore, procyanidin extracts, a mixture of polyphenols, inhibited NF- κ B (p65) translocation in lipopolysaccharide-stimulated macrophages [39].…”