Life sciences · 2021
Antitumor effect of dimethyl itaconate on thymic carcinoma by targeting LDHA-mTOR axis.
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Hayashi Keitaro, Nakazato Yoshimasa, Ouchi Motoshi, Fujita Tomoe, Endou Hitoshi, Chida Masayuki
Аннотация
AIMS: Thymic carcinoma is a rare type of cancer without an established standard pharmaceutical treatment. This study investigated the antitumor effect of dimethyl itaconate (DI), a cell-permeable derivative of itaconate, on human thymic carcinoma cell line.
MAIN METHODS: Human thymic carcinoma cell line Ty82 was used to evaluate the effect of DI on cell viability. Western blotting and immunohistochemistry were performed to determine the molecular mechanism of antitumor effects of DI on Ty82.
KEY FINDINGS: DI suppressed cell growth and promoted apoptosis of Ty82. The suppressive effect of DI on Ty82 was mediated by the downregulation of lactate dehydrogenase A (LDHA), and the subsequent decrease in the activity of mechanistic target of rapamycin (mTOR). DI exhibited synergistic antitumor effects with a specific inhibitor of large neutral amino acid transporter 1 (LAT1), an amino acid transporter currently being investigated as a novel target for cancer therapy.
SIGNIFICANCE: Our findings demonstrate that DI is a novel potential strategy for thymic carcinoma treatment.
MAIN METHODS: Human thymic carcinoma cell line Ty82 was used to evaluate the effect of DI on cell viability. Western blotting and immunohistochemistry were performed to determine the molecular mechanism of antitumor effects of DI on Ty82.
KEY FINDINGS: DI suppressed cell growth and promoted apoptosis of Ty82. The suppressive effect of DI on Ty82 was mediated by the downregulation of lactate dehydrogenase A (LDHA), and the subsequent decrease in the activity of mechanistic target of rapamycin (mTOR). DI exhibited synergistic antitumor effects with a specific inhibitor of large neutral amino acid transporter 1 (LAT1), an amino acid transporter currently being investigated as a novel target for cancer therapy.
SIGNIFICANCE: Our findings demonstrate that DI is a novel potential strategy for thymic carcinoma treatment.