New cancer treatment strategy using combination of green tea catechins and anticancer drugs

Abstract

Green tea is now recognized as the most effective cancer preventive beverage. In one study, 10 Japanese-size cups of green tea daily supplemented with tablets of green tea extract limited the recurrence of colorectal polyps in humans to 50%. Thus, cancer patients who consume green tea and take anticancer drugs will have double prevention. We studied the effects of combining ())-epigallocatechin gallate (EGCG) and anticancer drugs, focusing on inhibition of cell growth and induction of apoptosis. Numerous anticancer drugs, such as tamoxifen, COX-2 inhibitors, and retinoids were used for the experiments, and the combination of EGCG and COX-2 inhibitors consistently induced the enhancement of apoptosis. To study the mechanism of the enhancement, we paid special attention to the enhanced expressions of DDIT3 (growth arrest and DNA damage-inducible 153, GADD153), GADD45A, and CDKN1A (p21 ⁄ WAF1 ⁄ CIP1) genes, based on our previous evidence that a combination of EGCG and sulindac specifically induced upregulated expression of GADD153 and p21 genes in PC-9 lung cancer cells. The synergistic enhancements of apoptosis and GADD153 gene expression in human non-small cell lung cancer cells by the combination of EGCG and celecoxib were mediated through the activation of the MAPK signaling pathway. This article reviews the synergistic enhancement of apoptosis, gene expression, and anticancer effects using various combinations of EGCG and anticancer drugs, including the combination of ())-epicatechin (EC) and curcumin. Based on the evidence, we present a new concept: green tea catechins as synergists with anticancer drugs. (Cancer Sci 2011; 102: 317-323) ''C ancer chemoprevention'' was defined in 1976,(1) and Michael Sporn (2) introduced the term ''combination cancer chemoprevention'' in the journal Nature in 1980. He defined the term as the combined use of several drugs with different mechanisms of action exerting marked synergistic preventive effects. In 1983, we began to study the cancer preventive activity of green tea catechins.(3,4) Green tea extract chemically contains at least four tea catechins: EGCG, ECG, EGC, and EC. The first three catechins induce cancer preventive activities, whereas EC is inactive.(5) We first reported that combinations with the active catechins and inactive EC induced synergistic effects on induction of apoptosis and inhibition of cell growth of human lung cancer cell line PC-9, and inhibition of TNF-a release from BALB ⁄ 3T3 cells treated with okadaic acid, a tumor promoter.(6) This suggests that whole green tea, which is a mixture of green tea catechins, is a more effective and practical cancer preventive than green tea catechins alone.(6) Using tritium ( 3 H)-EGCG we showed that EC induced the enhanced incorporation of 3 H-EGCG and other active green tea catechins into cells.(6) In addition, we recently showed that drinking 10 cups of green tea supplemented with green tea tablets significantly (50%) prevented recurrence of colorectal adenomas in patients who had received polypectomy 1 yea...

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy

“…As explained in detail below, EGCG has been proposed as potential adjuvant for cancer therapy. 3 Abbreviations: 5-FU, 5-fluorouracil; ATO, arsenic trioxide; CP, cisplatin; DNR, daunorubicin; DNROL, daunorubicinol; DOX, doxorubicin; EGCG, epigallocatechin-3-gallate; HBMEC, human brain microvascular endothelial cells; HRPC, hormone refractory prostate cancer; HNE, hydroxynonenal; IL, interleukin; IR, ionizing radiation; ROS, reactive oxygen species; TSA, trichostatin A.…”

“…2 Moreover, its potential use as chemo/radiosensitizer of cancer cells has been proposed, and synergistic effects with different cancer treatments have been shown. 3 In addition, antioxidant and anti-inflammatory properties of EGCG have been associated with the amelioration of adverse side effects derived from cancer therapy. 4 ( Fig.…”

A comparative study of the antioxidant, antimicrobial, cytotoxic and thrombolytic potential of the fruits and leaves of Spondias dulcis

“…About 2.0 mL of methanol solution of each extract at different concentration (2,4,6,8,10 µg/mL) were mixed with 3.0 mL of DPPH methanol solution (20 µg/mL). After an incubation period of 30 min, the absorbance was measured at 517 nm against methanol as blank by using a UV-visible spectrophotometer.…”

“…Several studies revealed that antioxidants are related to other bioactivities e.g. in vitro cytotoxicity in tumor cell and in vivo cytotoxicity in experimental animals and anticarcinogenesis [18][19][20] . Almost all currently available thrombolytic regimens have some vital shortcomings including limited fibrin specificity, noteworthy bleeding tendency and large dose requirement.…”

Tea and human health: biomedical functions of tea active components and current issues

“…The inhibitory action was associated with the synergistic induction of apoptosis. Suganuma et al (2011) further studied the mechanism of the synergic action and found that a combination of EGCG and sulindac specifically induced upregulated expression of GADD153 and p21 genes in PC-9 lung cancer cells, and the synergistic enhancements of apoptosis and GADD153 gene expression in human non-small cell lung cancer cells by the combination of EGCG and celecoxib were mediated through the activation of the mitogen-activated protein kinases (MAPK) signaling pathway. Based on previous evidence, they presented a new concept: green tea catechins as synergists with anticancer drugs.…”