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.