Tea and Its Components Prevent Cancer: A Review of the Redox-Related Mechanism

Abstract

Cancer is a worldwide epidemic and represents a major threat to human health and survival. Reactive oxygen species (ROS) play a dual role in cancer cells, which includes both promoting and inhibiting carcinogenesis. Tea remains one of the most prevalent beverages consumed due in part to its anti- or pro-oxidative properties. The active compounds in tea, particularly tea polyphenols, can directly or indirectly scavenge ROS to reduce oncogenesis and cancerometastasis. Interestingly, the excessive levels of ROS induced by consuming tea could induce programmed cell death (PCD) or non-PCD of cancer cells. On the basis of illustrating the relationship between ROS and cancer, the current review discusses the composition and efficacy of tea including the redox-relative (including anti-oxidative and pro-oxidative activity) mechanisms and their role along with other components in preventing and treating cancer. This information will highlight the basis for the clinical utilization of tea extracts in the prevention or treatment of cancer in the future.

Keywords: ROS homeostasis; anti-oxidative; cancer; pro-oxidative; tea and its components.

Figure 1

Reactive oxygen species (ROS) generation and homeostasis. The endogenous generation of ROS is primarily derived from the mitochondrial electron transport chain (ETC), including a family of membrane-bound NADPH oxidases (NOXs) and 5-Lipoxygenase (5-LOX). As a precursor of H₂O₂ and OH^•, O₂⁻can be converted into H₂O₂ by three isoforms of superoxide dismutases (SOD) (i.e., SOD1, 2, and 3) that locate in the cytoplasm, mitochondria matrix, and extracellular matrix. O₂⁻ reacts with nitric oxide (NO), and produces peroxynitrite (ONOO⁻), which will decrease antioxidant capacity. OH^• is the production of H₂O₂ undergoing Fenton chemistry, and it owns the strongest chemistry activity, which can cause damage to biomolecules (such as DNA damage, lipid peroxidation, and protein denaturation). In addition, H₂O₂ can be catalyzed to H₂O by peroxiredoxins (PRXs), glutathione peroxidases (GPXs), and catalase (CAT). Glutathione (GSH) is the main non-enzymatic antioxidant in cells, and plays an important role in the degradation of H₂O₂. Two molecules of GSH are oxidized by H₂O₂ through GPX, and are converted into glutathione disulfide (GSSG), and then are regenerated GSH via glutathione reductase (GR) and NADPH.

Figure 2

Anti-cancer mechanisms of tea by regulating ROS homeostasis. Anti-oxidative activity of tea. Tea polyphenols can directly scavenge ROS by depending on its B and D ring of the galloyl group, and the phenolic hydroxyl group. Tea can also indirectly eliminate ROS through improving anti-oxidative enzymes activities, decreasing the effects of the oxidases, decreasing by-products (including MDA, HNE, and 8-oxo-dG) formation, and decreasing the inflammatory reaction, which involves the regulation of Nrf2 and NF-κB signaling pathways. Moreover, tea can regulate the drug-metabolizing pathways or become a chelating agent to scavenge ROS. Pro-oxidative activity of tea. With pro-oxidative activity, tea can selectively induce programmed cell death (PCD) or non-PCD of cancer cells, and it is considered as a potential anti-cancer candidate. PCD of cancer cells includes ROS-induced apoptosis or autophagy by mitochondrial dysfunction, the reduction of Trx/TrxR, and ROS-induced hyperactivation of p38, JNK, and p53, which activate the expression of downstream apoptotic proteins (such as Bax, caspase-3, and caspase-9). In addition, tea can induce non-PCD of cancer cells through ROS-induced DNA degradation by endogenous copper and ROS-mediated lysosomal membrane permeabilization.