抄録
Growth of cancer cells is more highly dependent on various types of amino acids than that of normal cells, and thus prevention of amino acid requirement has been recognized as strategies for cancer therapies. In this study, we found that deprivation of cysteine (Cys) in culturing media prevented the growth of various types of human cancer cell lines. Cys is easily converted to cystine (Cys–Cys) in media and uptaken into cells by cystine/glutamate transporter (xCT). The incorporated Cys–Cys is decomposed into Cys, and used for synthesis of glutathione that suppresses reactive oxygen species-induced cell damage. Therefore, we examined whether a selective xCT inhibitor erastin prevented the growth of human cancer cell lines. As a result, erastin significantly prevented the proliferation of various types of human cancer cells. Among them, MDA-MB-231 breast cancer cells were identified as the most erastin-sensitive cells. To investigate the ability of erastin to prevent growth of tumor in mice, MDA-MB-231 breast cancer cells were implanted into BALB/c nude female mice kept under standardized light/dark cycle conditions. The growth of tumor implanted in mice was significantly suppressed by administration of erastin during the light phase, whereas its administration during the dark phase failed to suppress the tumor growth. The dosing time-dependency of erastin-induced cystine/ cysteine deprivation was closely related to that of its anti-tumor effects. Our present findings suggest that the anti-tumor efficacy of erastin in tumor-bearing mice is improved by optimizing the dosing schedule.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 1921-1925 |
| ページ数 | 5 |
| ジャーナル | Biological and Pharmaceutical Bulletin |
| 巻 | 42 |
| 発行部数 | 11 |
| DOI | |
| 出版物ステータス | 出版済み - 1 1 2019 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmaceutical Science
これを引用
Dosing Time-Dependent Changes in the Anti-tumor Effect of xCT Inhibitor Erastin in Human Breast Cancer Xenograft Mice. / Shiromizu, Shoya; Yamauchi, Tomoaki; Kusunose, Naoki; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro.
：: Biological and Pharmaceutical Bulletin, 巻 42, 番号 11, 01.01.2019, p. 1921-1925.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Dosing Time-Dependent Changes in the Anti-tumor Effect of xCT Inhibitor Erastin in Human Breast Cancer Xenograft Mice
AU - Shiromizu, Shoya
AU - Yamauchi, Tomoaki
AU - Kusunose, Naoki
AU - Matsunaga, Naoya
AU - Koyanagi, Satoru
AU - Ohdo, Shigehiro
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Growth of cancer cells is more highly dependent on various types of amino acids than that of normal cells, and thus prevention of amino acid requirement has been recognized as strategies for cancer therapies. In this study, we found that deprivation of cysteine (Cys) in culturing media prevented the growth of various types of human cancer cell lines. Cys is easily converted to cystine (Cys–Cys) in media and uptaken into cells by cystine/glutamate transporter (xCT). The incorporated Cys–Cys is decomposed into Cys, and used for synthesis of glutathione that suppresses reactive oxygen species-induced cell damage. Therefore, we examined whether a selective xCT inhibitor erastin prevented the growth of human cancer cell lines. As a result, erastin significantly prevented the proliferation of various types of human cancer cells. Among them, MDA-MB-231 breast cancer cells were identified as the most erastin-sensitive cells. To investigate the ability of erastin to prevent growth of tumor in mice, MDA-MB-231 breast cancer cells were implanted into BALB/c nude female mice kept under standardized light/dark cycle conditions. The growth of tumor implanted in mice was significantly suppressed by administration of erastin during the light phase, whereas its administration during the dark phase failed to suppress the tumor growth. The dosing time-dependency of erastin-induced cystine/ cysteine deprivation was closely related to that of its anti-tumor effects. Our present findings suggest that the anti-tumor efficacy of erastin in tumor-bearing mice is improved by optimizing the dosing schedule.
AB - Growth of cancer cells is more highly dependent on various types of amino acids than that of normal cells, and thus prevention of amino acid requirement has been recognized as strategies for cancer therapies. In this study, we found that deprivation of cysteine (Cys) in culturing media prevented the growth of various types of human cancer cell lines. Cys is easily converted to cystine (Cys–Cys) in media and uptaken into cells by cystine/glutamate transporter (xCT). The incorporated Cys–Cys is decomposed into Cys, and used for synthesis of glutathione that suppresses reactive oxygen species-induced cell damage. Therefore, we examined whether a selective xCT inhibitor erastin prevented the growth of human cancer cell lines. As a result, erastin significantly prevented the proliferation of various types of human cancer cells. Among them, MDA-MB-231 breast cancer cells were identified as the most erastin-sensitive cells. To investigate the ability of erastin to prevent growth of tumor in mice, MDA-MB-231 breast cancer cells were implanted into BALB/c nude female mice kept under standardized light/dark cycle conditions. The growth of tumor implanted in mice was significantly suppressed by administration of erastin during the light phase, whereas its administration during the dark phase failed to suppress the tumor growth. The dosing time-dependency of erastin-induced cystine/ cysteine deprivation was closely related to that of its anti-tumor effects. Our present findings suggest that the anti-tumor efficacy of erastin in tumor-bearing mice is improved by optimizing the dosing schedule.
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UR - http://www.scopus.com/inward/citedby.url?scp=85074549105&partnerID=8YFLogxK
U2 - 10.1248/bpb.b19-00546
DO - 10.1248/bpb.b19-00546
M3 - Article
C2 - 31685775
AN - SCOPUS:85074549105
VL - 42
SP - 1921
EP - 1925
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 11
ER -