The Effect of Taurine, a Novel Biochemical Modulator, on the Antitumor Activity of Doxorubicin

Abstract

In cancer therapy, novel chemotherapeutic agents are being developed continually, 1) however, cancer-induced lethality is still high in many countries because of recalcitrant tumors and the appearance of resistant tumors. Furthermore, adverse reactions by antitumor drugs not only inhibit the therapeutic index but also require the use of combined agents to decrease these adverse reactions and the quality of life (QOL) of patients can worsen. While the development of novel antitumor drugs is a long and costly process, increasing the effectiveness of current therapies is also very important and should be addressed in clinical trials. As an example combined medicines, such as p-glycoprotein inhibitor in resistant tumors, have been used to increase the effectiveness of current antitumor agents. [2][3][4] From the viewpoint of biochemical modulation, combined medicines such as Tegaful have been applied in clinical therapy. However, it has been reported that some combined therapies increase the adverse effects of antitumor drugs as the antitumor effect increases, 5) and effective enhancement of the therapeutic index is not achieved. Furthermore, the QOL of patients can be affected negatively by many medicines. It is hoped to increase antitumor agent activity by combining antitumor therapies with foods that do not show adverse reactions or decrease QOL.From such a viewpoint, it was reported previously that theanine, an amino acid peculiar to green tea, has properties to increase the efficacy of doxorubicin (DOX) as an antitumor drug. 6) This action is due to the glutamate transporter expressed in the tumor cell membrane and is dependent on the influx inhibition of glutamate by theanine inhibition of this transporter and the resulting decrease in glutathione (GSH) synthesis. 7)Theanine did not increase DOX-induced adverse reactions in normal tissue, whereas reduced its adverse effects, and was therefore effective in enhancing the antitumor effect while decreasing the adverse effects of antitumor drugs. It is expected that there are other compounds with similar effectiveness, such as an amino acids or peptides, in other foods.Taurine (2-amino ethanesulfonic acid) is a major amino acid in fish and is found in all mammalian tissues. In clinical therapy, taurine is used to protect the liver and improve function with congestive cardiac failure. This study investigated the effect of taurine on the tumor cell permeability of DOX in vitro, studied its action on the antitumor effect of DOX in vivo, and elucidated the novel effect of taurine to increase DOX-induced antitumor activity. MATERIALS AND METHODSChemicals Taurine, b-alanine was purchased from Wako Pure Chemical Industries, Ltd. (Tokyo, Japan). DOX 10 mg/vial (Adriacin), was purchased from Kyowa Fermentation, Inc. (Tokyo, Japan). RPMI 1640 medium was purchased from Nissui Pharmaceutical Co., Ltd. (Tokyo, Japan). [ 3 H]-Taurine (9.5 MBq/mmol) was purchased from Amersham (Tokyo, Japan). Scintillation cocktail Scientisol Ex-H ® , balanine, and g-amino butyric acid (GABA) wer...

Mechanism of taurine-induced apoptosis in human colon cancer cells

“…It has been reported that Tau has an efficacy-enhancing and toxicity-reducing effect on cyclophosphamide [22] and improve the efficacy of cyclophosphamide in the treatment of leukemia [23]. Tau can improve the anti-tumor efficacy of doxorubicin without increasing the side effects [24]. (ii) Tau inhibits cancer growth by improving the antioxidant capacity in vivo.…”

Taurine: a novel tumor marker for enhanced detection of breast cancer among female patients

“…Recently, a lot of researches through light on the use of taurilidine as antineoplastic drug in human bladder carcinoma [49] gastro-intestinal cancer [50] to prevent the development of lung metastasis [51], and it may offer additional therapeutic option in patient with colon adenocarcinoma [51], as a useful modulator to enhance the therapeutic index of some antitumor agents [16], in the treatment of oesophageal cancer [14], in treatment of malignant mesothelioma [52] and as a biomarker in non-muscle invasive bladder cancer [53]. In conclusion and based on the present study we can strongly suggest the assessment of taurine level in sera of patients with high risk of breast cancer and in the early diagnosis of any malignant changes in the breast.…”

“…Taurine and its derivatives such as taurolidine and taurochloramin were found to display antineoplastic effect both in vitro and in vivo; through suppressing cell proliferation, enhancement of tumor cell apoptosis [14][15][16][17][18][19][20][21], and through an antiangiogenic effects [15,22] while enhancing the therapeutic index of some antitumer agent [16]. Recently taurine level used as early marker in hepatocellular carcinoma (HCC) [17] and in cancer uterus [18].…”

Improvements of Doxorubicin-Induced Antitumor Activity and Adverse Reaction by Combined Citrulline

“…Previously, we reported improved DOX-induced antitumor activity using the food components caffeine, theanine, and cucurbitacins. [6][7][8][9][10][11][12][13][14][15] It appeared that these effects were mediated by increased DOX concentration in the tumors, which suppress DOX efflux from tumor cells. In contrast, linalool promoted DOX influx into tumor cells and enhanced its activity by acting on the Na + -dependent nucleoside transporter (CNT) 3.…”