Tea remains one of the most prevalent beverages consumed due in part to its physiological properties. The active compounds in tea, including tea polyphenols, tea polysaccharides, L-theanine, tea pigments, caffeine and other minor composition, can directly or indirectly reduce oncogenesis and cancerometastasis. Interestingly, the different types of tea (such as unfermented green tea, partially fermented oolong tea, and fully fermented black tea or pu-erh tea) have the different anti-cancer property.
The major tea-producing countries are China, India, Japan, Sri Lanka, Indonesia, and Central African countries . The argument that tea is a cancer preventive agent is no longer new. A pioneering study in the mid-1990s summarized the available epidemiologic information and found that tea consumption is likely to have beneficial effects on reducing the cancer risk in some people . Recently, a meta-analysis found an inverse association between tea consumption and cancer risk . And, some evidence does not support the hypothesis that tea can reduce the risk of cancer . The above conflicting results could be due to variations in the types, dosage, and drinking manner of tea. In fact, the components and quality of tea are variable by the category, growth environment, storage time, and method of production, which will affect the original beneficial effects of tea.
Tea polyphenols are one of the most important ingredients in regulating the redox balance of tea. Tea polyphenols can reduce the incidence and development of tumors in the stomach, intestines, liver, lungs, skin and other parts of the whole body . Catechins are the most abundant polyphenols in tea, mainly including epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC) . Among them, EGCG is the major catechin in tea, and may account for 50–80% of the total catechins .
Tea polyphenols could decrease the risk of skin cancer through inhibiting ultraviolet light B (UVB)-induced oxidative stress, such as the depletion of antioxidant enzymes, lipid oxidation, and the infiltration of inflammatory cells . In a two-stage model of diethylnitrosamine (DEN)/phenobarbital (PB)-induced hepatocarcinogenesis of Sprague-Dawley rats, oral gavage of tea polyphenols five times weekly could significantly increase the total antioxidant capacity (T-AOC) and glutathione peroxidase (GPX) activity in livers . In the multistage mouse skin carcinogenesis model, peracetylated EGCG treatment could decrease the expression of oxidative enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 . In addition, tea polyphenols show a pro-oxidative activity. EGCG induced oxidative stress and mitochondrial dysfunction, and played an anti-cancer role in oral cancer .
In addition to acting as preventive agents, tea polyphenols can also be used as adjuvant therapies for various cancers. When EGCG is combined with a conventional cancer therapy additive, synergistic effects have been proposed, which are mainly due to its anti-inflammatory and anti-oxidative activities that improve the side effects during cancer treatment . Zhang et al. found that the administration of 400 mg EGCC three times daily potentiated the efficacy of radiotherapy in patients . However, EGCG also has antagonistic interactions with PS-341, which will limit its clinical use. PS-341 is an anti-myeloma drug which activity would be blocked by EGCG through vicinal diols on polyphenols interacting with the boronic acid of PS-341 . As a consequence, pre-clinical studies on tea polyphenols (particularly on the bioactive utilization, mechanism of action, and safety of EGCG) need to be carried out.
Tea polysaccharides (TPS) are a group of hetero-polysaccharides bonded with proteins . Yang et al. reported that TPS (400–800 μg/mL) significantly improved the anti-oxidative capacity in a dose-dependent manner, and inhibited the cancerometastasis of gastric cancer in mice . Selenium (Se)-containing TPS (IC50 of 140.1 μg/mL) induced ROS generation, which made cells undergo G2/M phase arrest and apoptosis and exhibited effective inhibition of human breast cancer MCF-7 cell growth . Moreover, compared with the utilization of doxorubicin (DOX) alone, a combination of TPS and DOX has a better suppression efficiency in lung cancer A549 cells .
L-theanine is a natural amino acid, which is found specifically in tea plants and makes up 1–2% of the dry weight of tea leaves . Liu et al. found that theanine and its derivates had no toxicity in mice . Recent studies have shown that, in addition to relieving depression, memory improvement, and neuroprotection , L-theanine may also have anti-tumor activities. Adriamycin (ADR) was used to efficiently treat Ehrlich ascites carcinoma cells and its side effects, such as reducing antioxidant enzyme activity and increasing the level of lipid peroxidation, can be alleviated by the combined utilization of L-theanine .
Tea pigments are the oxidized products of polyphenols and their derivatives in tea leaves, and mainly consist of theaflavins (TFs), thearubigins (TRs), and theabrownin . The composition of tea pigments in black tea are similar to that of the tea polyphenols in green tea, but the former is chemically stable and may be an ideal chemopreventive agent . In a rat liver precancerous lesion model, the treatment with tea pigments suppressed cancer biomarkers, such as glutathione S-transferase Pi (GST-Pi) mRNA and protein . Furthermore, in an in vivo trial on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis, treatment with 0.1% tea pigments reduced aberrant cryptic foci (ACF) and colonic tumor formation .
Caffeine, the most abundant alkaloid in tea, makes up 2–4% of the dry weight, and its structure is identified as 1,3,7-trimethylxanthine . Caffeine has been shown to have both positive and negative health effects. The cancer preventative effects of caffeine in rodent hepatocellular carcinoma (HCC) models have also been demonstrated . Chronic caffeine ingestion inhibited rat breast cancer, neither by interfering with the high prolactin levels that is a necessary step in murine tumor development, nor by causing hypocaloric intake . However, an in vivo trial showed that the rats consuming caffeine and unsaturated fat had the earliest tumor development and the most multiple tumor occurrence .
Along with studying the different components of tea, studies should also be undertaken to analyze their anti-cancer properties. Generally, tea is divided into three main types based on production, namely unfermented green tea, partially fermented oolong tea, and fully fermented black tea or pu-erh tea . There are not a consistent conclusion on the anti-oxidant capacity of tea polyphenols derived from the differently produced teas. The individual effects of green tea, black tea, and oolong tea on cancer are difficult to confirm using epidemiological research, mainly due to many consuming several tea types . However, it appears that when comparing the anti-cancer effects between green tea and black tea, the former is more efficient . This can be associated with the stronger antioxidant capacity and protective effects of green tea . Record and Dreosti reported that treatment with black tea provided more protection than green tea in solar irradiation-induced skin cancer in hairless mice . Until now, there has been no direct evidence that oolong tea, a semi-fermented tea, has the ability to fight cancer. Only one in vitro experiment showed that oolong tea has the worst inhibiting effect on the invasion and proliferation of AH109A compared with green and black teas .