theanine and Neoplasm-Metastasis

Prostate cancer (PCa) is a very prevalent male-specific malignancy; most PCa patients eventually die as a result of metastasis. L-theanine (C7H14N2O3), a nonprotein amino acid derivative from green tea leaves, has been demonstrated to act as an anticarcinogen through proapoptotic and antiproliferative effects. However, the antimetastatic effect of L-theanine in tumor cells and its underlying mechanism are still unclear. Here, we found that L-theanine could suppress invasion, migration, and increase cell-cell adhesion of prostate cancer cells in vitro and in vivo. We also found that L-theanine could inhibit the epithelial-mesenchymal transition process in PCa. Our study revealed that L-theanine could downregulate MMP9, N-cadherin, Vimentin, Snail, and upregulate E-cadherin. Furthermore, L-theanine suppressed the transcription of MMP9 and Snail by significantly inhibiting the ERK/NF-κB signaling pathway and the binding activity of p65 to the promoter regions of MMP9 and Snail. All of these findings suggest that L-theanine has therapeutic potential for metastatic PCa and may be considered a promising candidate for antimetastatic therapy of prostate cancer.

Topics: Animals; Antineoplastic Agents; Cadherins; Cell Movement; Down-Regulation; Epithelial-Mesenchymal Transition; Glutamates; Humans; Male; Matrix Metalloproteinase 9; Mice; Neoplasm Metastasis; NF-kappa B; PC-3 Cells; Prostatic Neoplasms; Signal Transduction; Snail Family Transcription Factors; Tea; Vimentin

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