Cancer: Breast, pancreatic, lung, colorectal
Action: Chemo-preventive effects, metastasis
(-)-Epigallocatechin gallate (EGCG) is isolated from Camellia sinensis [(L.) Kuntze].
Epidemiological evidence suggests tea (Camellia sinensis L.) has chemo-preventive effects against various tumors. (-)-Epigallocatechin gallate (EGCG), a catechin polyphenol compound, represents the main ingredient of green tea extract and is chemo-preventive and an anti-oxidant. EGCG shows growth inhibition of various cancer cell lines, such as lung, mammary, and stomach.
Breast Cancer, Colorectal Cancer
Although EGCG has been shown to be growth-inhibitory in a number of tumor cell lines, it is not clear whether the effect is cancer-specific. The effect of EGCG on the growth of SV40 virally transformed WI38 human fibroblasts (WI38VA) was compared with that of normal WI38 cells. The IC50 value of EGCG was estimated to be 120 and 10 microM for WI38 and WI38VA cells, respectively. Similar differential growth inhibition was also observed between a human colorectal cancer cell line (Caco-2), a breast cancer cell line (Hs578T) and their respective normal counterparts.
EGCG at a concentration range of 40-200 microM induced a significant amount of apoptosis in WI38VA cultures, but not in WI38 cultures, as determined by terminal deoxynucleotidyl transferase assay. It is possible that differential modulation of certain genes, such as c-fos and c-myc, may cause differential effects of EGCG on the growth and death of cancer cells (Chen et al., 1998).
Breast Cancer
Green tea contains many polyphenols, including epigallocatechin-3 gallate (EGCG), which possess anti-oxidant qualities. Reduction of chemically-induced mammary gland carcinogenesis by green tea in a carcinogen-induced rat model has been suggested previously, but the results reported were not statistically significant. Green tea significantly increased mean latency to the first tumor, and reduced tumor burden and number of invasive tumors per tumor-bearing animal; however, it did not affect tumor number in female rats.
Furthermore, we show that proliferation and/or viability of cultured Hs578T and MDA-MB-231 estrogen receptor-negative breast cancer cell lines was reduced by EGCG treatment. Similar negative effects on proliferation were observed with the DMBA-transformed D3-1 cell line. Growth inhibition of Hs578T cells correlated with induction of p27Kip1 cyclin-dependent kinase inhibitor (CKI) expression.
Thus, green tea had significant chemo-preventive effects on carcinogen-induced mammary tumorigenesis in female S-D rats. In culture, inhibition of human breast cancer cell proliferation by EGCG was mediated in part via induction of the p27Kip1 (Kavanagh et al., 2001).
Pancreatic Cancer
The in vitro anti-tumoral properties of EGCG were investigated in human PDAC (pancreatic ductal adenocarcinoma) cells PancTu-I, Panc1, Panc89 and BxPC3 in comparison with the effects of two minor components of green tea catechins, catechin gallate (CG) and epicatechin gallate (ECG). It was found that all three catechins inhibited proliferation of PDAC cells in a dose- and time-dependent manner.
Interestingly, CG and ECG exerted much stronger anti-proliferative effects than EGCG. Importantly, catechins, in particular ECG, inhibited TNFα-induced activation of NF-κB and consequently secretion of pro-inflammatory and invasion promoting proteins like IL-8 and uPA.
Overall, these data show that green tea catechins ECG and CG exhibit potent and much stronger anti-proliferative and anti-inflammatory activities on PDAC cells than the most studied catechin EGCG (KŸrbitz et al., 2011).
Okabe et al. (1997) assessed the ability of EGCG to inhibit HGF signaling in the immortalized, nontumorigenic breast cell line, MCF10A, and the invasive breast carcinoma cell line, MDA-MB-231. The ability of alternative green tea catechins to inhibit HGF-induced signaling and motility was investigated. (-)-Epicatechin-3-gallate (ECG) functioned similarly to EGCG by completely blocking HGF-induced signaling as low as 0.6 muM and motility at 5 muM in MCF10A cells; whereas, (-)-epicatechin (EC) was unable to inhibit HGF-induced events at any concentration tested. (-)-Epigallocatechin (EGC), however, completely repressed HGF-induced AKT and ERK phosphorylation at concentrations of 10 and 20 muM, but was incapable of blocking Met activation. Despite these observations, EGC did inhibit HGF-induced motility in MCF10A cells at 10 muM.
Metastsis Inhibition
These observations suggest that the R1 galloyl and the R2 hydroxyl groups are important in mediating the green tea catechins' inhibitory effect towards HGF/Met signaling. These combined in vitro studies reveal the possible benefits of green tea polyphenols as cancer therapeutic agents to inhibit Met signaling and potentially block invasive cancer growth (Bigelow et al., 2006).
Colorectal Cancer
Panaxadiol (PD) is a purified sapogenin of ginseng saponins, which exhibits anti-cancer activity. Epigallocatechin gallate (EGCG), a major catechin in green tea, is a strong botanical anti-oxidant. Effects of selected compounds on HCT-116 and SW-480 human colorectal cancer cells were evaluated by a modified trichrome stain cell proliferation analysis. Cell-cycle distribution and apoptotic effects were analyzed by flow cytometry after staining with PI/RNase or annexin V/PI. Cell growth was suppressed after treatment with PD (10 and 20 µm) for 48 h. When PD (10 and 20 µm) was combined with EGCG (10, 20, and 30 µm), significantly enhanced anti-proliferative effects were observed in both cell lines.
Combining 20 µm of PD with 20 and 30 µm of EGCG significantly decreased S-phase fractions of cells. In the apoptotic assay, the combination of PD and EGCG significantly increased the percentage of apoptotic cells compared with PD alone (p < 0.01).
Data from this study suggested that apoptosis might play an important role in the EGCG-enhanced anti-proliferative effects of PD on human colorectal cancer cells (Du et al., 2013).
Action: Anti-inflammatory, antioxidant
Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review.
Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use.
The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy.
Cancer: Pancreatic ductal adenocarcinoma
Action: Anti-proliferative and anti-inflammatory
In the present study, Kürbitz et al., (2011) investigated the in vitro anti-tumoral properties of EGCG on human PDAC (pancreatic ductal adenocarcinoma) cells PancTu-I, Panc1, Panc89 and BxPC3 in comparison with the effects of two minor components of green tea catechins catechin gallate (CG) and epicatechin gallate (ECG). We found that all three catechins inhibited proliferation of PDAC cells in a dose- and time-dependent manner. Interestingly, CG and ECG exerted much stronger anti-proliferative effects than EGCG. Western blot analyses performed with PancTu-I cells revealed catechin-mediated modulation of cell cycle regulatory proteins (cyclins, cyclin-dependent kinases [CDK], CDK inhibitors). Again, these effects were clearly more pronounced in CG or ECG than in EGCG treated cells. Importantly, catechins, in particular ECG, inhibited TNFα-induced activation of NF-κB and consequently secretion of pro-inflammatory and invasion promoting proteins like IL-8 and uPA. Overall, our data show that green tea catechins ECG and CG exhibit potent and much stronger anti-proliferative and anti-inflammatory activities on PDAC cells than the most studied catechin EGCG.
References
Du GJ, Wang CZ, Qi LW, et al. (2013). The synergistic apoptotic interaction of panaxadiol and epigallocatechin gallate in human colorectal cancer cells. Phytother Res, 27(2):272-7. doi: 10.1002/ptr.4707.
Kürbitz C, Heise D, Redmer T, Goumas F, et al. Cancer Science. Online publication Jan 2011. DOI: 10.1111/j.1349-7006.2011.01870.x