theanine and Liver-Neoplasms

To explore the potential of theanine against cancer, we have studied the anticancer activities of theanine from tea and its semisynthesized derivative, (R)-2-(6,8-dibromo-2-oxo-2H-chromene-3-carboxamido)-5-(ethylamino)-5-oxopentanoic ethyl ester (DTBrC), in in vitro, ex vivo, and in vivo models of human hepatocellular carcinoma (HHC). Theanine and DTBrC displayed inhibitory effects on the growth and migration of HHC cells in vitro, ex vivo, and in vivo. Theanine and DTBrC significantly enhanced the repression of HHC cell growth in combination with anticancer drug pirarubicin. Theanine and DTBrC completely suppressed HGF- and EGF+HGF-induced migration with a reduction of p53 tumor suppressor level and enhanced the p53 protein expression in HHC cells. The Akt and NF-κB knockdown greatly reduced cancer cell migration with a decrease in CD44 expression. DTBrC and theanine significantly repressed the protein expressions in the Met/EGFR/VEGFR-Akt/NF-κB pathways, which might be the mechanism for their biologic effects.

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Movement; ErbB Receptors; Female; Glutamates; Humans; Liver Neoplasms; Molecular Structure; NF-kappa B; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-met; Rats; Rats, Sprague-Dawley; Receptors, Vascular Endothelial Growth Factor; Signal Transduction

The content of the biologically active amino acid theanine in 15 commercial black, green, specialty, and herbal tea leaves was determined as the 2,4-dinitrophenyltheanine derivative (DNP-theanine) by a validated HPLC method. To define relative anticarcinogenic potencies of tea compounds and teas, nine green tea catechins, three black tea theaflavins, and theanine as well as aqueous and 80% ethanol/water extracts of the same tea leaves were evaluated for their ability to induce cell death in human cancer and normal cells using a tetrazolium microculture (MTT) assay. Compared to untreated controls, most catechins, theaflavins, theanine, and all tea extracts reduced the numbers of the following human cancer cell lines: breast (MCF-7), colon (HT-29), hepatoma (liver) (HepG2), and prostate (PC-3) as well as normal human liver cells (Chang). The growth of normal human lung (HEL299) cells was not inhibited. The destruction of cancer cells was also observed visually by reverse phase microscopy. Statistical analysis of the data showed that (a) the anticarcinogenic effects of tea compounds and of tea leaf extracts varied widely and were concentration dependent over the ranges from 50 to 400 microg/mL of tea compound and from 50 to 400 microg/g of tea solids; (b) the different cancer cells varied in their susceptibilities to destruction; (c) 80% ethanol/water extracts with higher levels of flavonoids determined by HPLC were in most cases more active than the corresponding water extracts; and (d) flavonoid levels of the teas did not directly correlate with anticarcinogenic activities. The findings extend related observations on the anticarcinogenic potential of tea ingredients and suggest that consumers may benefit more by drinking both green and black teas.

Topics: Anticarcinogenic Agents; Biflavonoids; Breast Neoplasms; Camellia sinensis; Catechin; Cell Death; Cell Line, Tumor; Glutamates; HT29 Cells; Humans; Liver Neoplasms; Male; Plant Leaves; Prostatic Neoplasms; Stomach Neoplasms; Structure-Activity Relationship; Tea

Theanine is a peculiar amino acid existing in green tea leaves, which was previously indicated to enhance the antitumor activity of doxorubicin. In the present study, the effect of combination of theanine with doxorubicin against hepatic metastasis of M5076 ovarian sarcoma was investigated. The primary tumor was significantly reduced by the combined treatment on M5076 transplanted (s.c.) mice. The liver weight of control mice increased to twice the normal level because of hepatic metastasis of M5076. In contrast, the injection of doxorubicin alone or theanine plus doxorubicin suppressed the increase in liver weight and inhibited hepatic metastasis. Moreover, the liver weights and metastasis scores demonstrated that theanine enhanced the inhibition of hepatic metastasis induced by doxorubicin. Furthermore, in vitro experiments indicated that theanine increased the intracellular concentration of doxorubicin remaining in M5076 cells. This action suggests that theanine leads the enhancement of the suppressive efficacy of doxorubicin on hepatic metastasis in vivo. Therefore, it was proved that theanine increased not only the antitumor activity on primary tumor but also the metastasis-suppressive efficacy of doxorubicin. The effect of theanine on the efficacy of antitumor agents is expected to be applicable in clinical cancer chemotherapy.

Topics: Analysis of Variance; Animals; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Glutamates; Liver Neoplasms; Male; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasm Transplantation; Organ Size; Ovarian Neoplasms; Sarcoma, Experimental