2-B-P-094 〇岡野 佑美¹、山内 智暁¹、吉田 優哉³、鶴田 朗人²、松永 直哉³、小柳 悟²、大戸 茂弘¹ Okano Yumi¹, Tomoaki Yamauchi¹, Yuya Yoshida³, Akito Tsuruta², Naoya Matsunaga³, Satoru Koyanagi², Shigehiro Ohdo^{1 1}九州大・院薬・薬剤学、²九州大・院薬・グローカルヘルスケア、³九州大・院薬・薬物動態学 ¹Dept. Pharmaceutics, Grad. Sch. Pharm., Kyushu Univ., ²Dept. Glocal Healthcare Sci., Grad. Sch. Pharm., Kyushu Univ., ³Dept. Clin. Pharmacokinetics, Grad. Sch. Pharm., Kyushu Univ. Cancer cells alter the activity of various metabolic pathways to sustain their abnormal proliferation. The reprogramming of amino acid metabolism is also observed in malignant cancer cells, characterized by enhancing de novo synthesis and/or extracellular uptake via upregulation of amino acid transporters. Our previous study demonstrated that cysteine was indispensable for proliferation of cancer cells and that the contents were increased in hepatic tumor tissues as compared with healthy liver. However, the pathological significance of this increased cysteine contents in hepatic tumor tissue has not been fully understood yet. In this study, we found that the growth ability of murine hepatoma cell line, BNL 1ME A.7 R.1 (BNL 1ME), but not of primary hepatocytes, was dependent on extracellular supply of cysteine. Cysteine deprivation induced the cell cycle arrest at G0/G1 phase in BNL 1ME cells, accompanying with decrease in the expression of Cyclin D1 and Cyclin D2 proteins. The cysteine deprivation-induced decrease in D-type cyclin expression was associated with the upregulation of eukaryotic translation initiation factor 4E binding protein (4E-BP1) that act as a translational repressor of Cyclin D1 and Cyclin D2 proteins. Although extracellularly supplied cysteine may be used for glutathione synthesis and enhance anti-oxidant capacity of cancer cells, our present findings also demonstrated its contribution to promote cell cycle progression of hepatic tumor cells.